Gastroparesis Medical Studies Update; Join and/or Keep Up With Clinical Trials

Source: Unknown

Source: Unknown

Source: On The Image but one of my favorites on how to explain Gastroparesis.









Clinical Trials - We Need Better Treatments

I apologize for taking so long to write an article. I, myself, have had a rough year like everyone else seemed to in the GP Community. I lost A LOT of friends last year in my support groups, people I started support groups with, and people I talked to regularly. I logged into Facebook this morning to check on my groups, as I've been sick with pneumonia on top of Gastroparesis for the past week and a half (before that, my husband and I were passing a respiratory virus back and forth) and found another one of my friends had died. She was someone I've known since I first started advocating for Gastroparesis. She was apart of the handful of women who helped start Gastroparesis support groups and build up the Gastroparesis Community. I wanted to dedicated this article to her, and the other friends I've lost. Last year, we lost 48 people. This year, so far, I think the total is four or five people. It's heartbreaking. We need better treatments. Having invasive "treatments" like feeding tubes, which can cause infections and worse, and then on the other end of the spectrum, medicine like Reglan, which can lead to irreversible, neurological disorders. We need medication to help our stomachs, to keep them from cramping so badly, to help them contract.

We need SOME kind of help. I'm so upset at watching my friends suffer and die. I get scared every time I throw up, wondering if it's going to be the last time - if this is the time I'm going to rupture my esophagus and die. I get panic attacks logging on to Facebook, scared I might read another one of my friends has passed away, which always upsets me right away, not only because they passed, but I feel like when I take breaks from Facebook, that I'm letting them down for not being online. I feel like I didn't get to say what I wanted to say to them before they passed. Most of that is on me. I've been not terrified to log into Facebook, but just



If you are interested in joining a clinical trial for Gastroparesis, The National Institute of Diabetes, Digestive, and Kidney Diseases are having people sign up for one now: https://www.niddk.nih.gov/health-information/digestive-diseases/gastroparesis/clinical-trials


Centerwatch has a long list of clinical trials that need volunteers as well: https://www.centerwatch.com/clinical-trials/listings/condition/72/gastroparesis/


ClinicalTrials.gov has a current trial happening as we speak: https://clinicaltrials.gov/ct2/show/NCT03500354

The Trial Says,

"Brief Summary:

Gastroparesis is a chronic, morbid and costly neuromuscular disorder of the stomach characterized by delayed gastric emptying in the absence of gross structural abnormalities. The periprandial symptoms associated with this disease can preclude adequate oral intake and often lead to weight loss and nutritional deficiencies 1. These manifestations are largely due to impaired gastric accommodation of meals and delayed transfer of food boluses from the stomach into the duodenum2. Consequently, the investigators hypothesize that dietary supplementation with a low volume, hypercaloric nutritional drink can help prevent malnutrition, decrease symptom burden and improve health-related quality of life in this population. Due to the paucity of such a supplement, the investigators developed a novel nutritional drink designed to maximize tolerability in patients with gastroparesis . This nutritional drink was tested on healthy volunteers (phase I) and passed the palatability test. The investigators now aim to test the tolerability of this drink on gastroparesis patients.

Condition or disease Intervention/treatment Phase
Gastroparesis Dietary Supplement: Nutrient drink Not Applicable

Detailed Description:

Primary objective:

To evaluate the safety and tolerability of the nutritional drink in gastroparesis patients.

Secondary objective:

To evaluate the efficacy of the nutritional drink in gastroparesis patients.

Study Procedures This study will be a pilot, open-label, trial in gastroparesis patients. A total of 20 patients will be recruited from the gastroenterology gastroparesis clinic. If the volunteer meets eligibility criteria, a co-investigator will contact the patient to schedule a study visit with a nutritionist and obtain a written consent. The contact and screening information of patients that are successfully recruited will be documented, placed in the participant's study folder and stored in a locked cabinet in the research unit. Any information documented during the screening process for patients who do not meet basic eligibility criteria or do not wish to participate will be immediately destroyed.

Patients will be given enough supply of the nutrition drink for (4 weeks) and asked to consume 200 ml of the drink three times daily. A follow-up call will be scheduled on day 2, day 7 and at the end of the study to make sure patients are tolerating the drink. Participants will be allowed to consume water and food as desired during the study period but will need to maintain an accurate food diary for at least one week prior to enrollment and during the study (at 2 weeks and at 4 weeks) along with weight measurements at baseline, 2 weeks, 4 weeks and 6 weeks. The participants will be asked to complete a palatability questionnaire. They will also complete the Gastroparesis Cardinal Symptom Index (GCSI) daily diary and the PROMISE scale prior to enrollment as a baseline for their symptoms and again at 2 weeks, 4 weeks (end of the study) and 6 weeks. Changes in these scales from baseline will determine the efficacy and possibly side effects of the nutritional drink.

Study duration and number of study visits required of research participants:

4 weeks, initial study visit with a nutritionist for screening and consenting followed by 3 follow-up phone calls on day 2, day 7 and at 4 weeks (the end of the study) and a final study visit at 6 weeks (2 weeks after finishing the study)


Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Pilot feasibility open-label study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Nutritional Drink in Gastroparesis
Estimated Study Start Date : February 1, 2019
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : August 2019




Primary Outcome Measures:

Tolerability will be measured by the Palatability Questionnaire at 2 days [ Time Frame: 2 days post-intervention ]

Patients will be given enough supply of the nutrition drink for 4 weeks and asked to consume 200 ml of the drink three times daily. A follow-up call will be scheduled on day 2 of the study to make sure patients are tolerating the drink.

Tolerability will be measured by the Palatability Questionnaire which rates six items on a scale of 1 to 5 (1= strongly disagree and 5= strongly agree. The six items are:
The formula/supplement tasted very good.
The formula/supplement tasted very bad.
I had no problems drinking the supplement.
Drinking the supplement made me feel ill.
I could drink more of this supplement anytime
I would never drink more of this supplement again

Tolerability will be measured by the Palatability Questionnaire at 7 days [ Time Frame: 7 days post-intervention ]

Patients will be given enough supply of the nutrition drink for 4 weeks and asked to consume 200 ml of the drink three times daily. A follow-up call will be scheduled on day 7 of the study to make sure patients are tolerating the drink.

Tolerability will be measured by the Palatability Questionnaire which rates six items on a scale of 1 to 5 (1= strongly disagree and 5= strongly agree. The six items are:
The formula/supplement tasted very good.
The formula/supplement tasted very bad.
I had no problems drinking the supplement.
Drinking the supplement made me feel ill.
I could drink more of this supplement anytime
I would never drink more of this supplement again

Tolerability will be measured by the Palatability Questionnaire at 4 weeks [ Time Frame: 4 weeks post-intervention ]

Patients will be given enough supply of the nutrition drink for 4 weeks and asked to consume 200 ml of the drink three times daily. A follow-up call will be scheduled at 4 weeks to make sure patients are tolerating the drink.

Tolerability will be measured by the Palatability Questionnaire which rates six items on a scale of 1 to 5 (1= strongly disagree and 5= strongly agree. The six items are:
The formula/supplement tasted very good.
The formula/supplement tasted very bad.
I had no problems drinking the supplement.
Drinking the supplement made me feel ill.
I could drink more of this supplement anytime
I would never drink more of this supplement again

Safety will be measured by the NIH PROMISE scale at baseline [ Time Frame: Baseline ]

This will be measured by the NIH PROMISE scale. This is a 10 point scale (0=none and 10= most severe) that rates the following symptoms:
Pain, especially in the abdomen, chest or back
Abdominal distension (bloating, sensation of excess gas)
Difficulty eating, sensation of food being stuck in the stomach.
Difficulty with bowel movements (constipation or straining)
Nausea and/or vomiting
Thirst
Weakness, lack of energy, fatigue, difficulty moving.

Safety will be measured by the NIH PROMISE scale at 2 weeks [ Time Frame: 2 weeks post-intervention ]

This will be measured by the NIH PROMISE scale. This is a 10 point scale (0=none and 10= most severe) that rates the following symptoms:
Pain, especially in the abdomen, chest or back
Abdominal distension (bloating, sensation of excess gas)
Difficulty eating, sensation of food being stuck in the stomach.
Difficulty with bowel movements (constipation or straining)
Nausea and/or vomiting
Thirst
Weakness, lack of energy, fatigue, difficulty moving.

Safety will be measured by the NIH PROMISE scale at 4 weeks [ Time Frame: 4 weeks post-intervention ]

This will be measured by the NIH PROMISE scale. This is a 10 point scale (0=none and 10= most severe) that rates the following symptoms:
Pain, especially in the abdomen, chest or back
Abdominal distension (bloating, sensation of excess gas)
Difficulty eating, sensation of food being stuck in the stomach.
Difficulty with bowel movements (constipation or straining)
Nausea and/or vomiting
Thirst
Weakness, lack of energy, fatigue, difficulty moving.

Safety will be measured by the NIH PROMISE scale at 6 weeks [ Time Frame: 6 weeks post-intervention ]

This will be measured by the NIH PROMISE scale. This is a 10 point scale (0=none and 10= most severe) that rates the following symptoms:
Pain, especially in the abdomen, chest or back
Abdominal distension (bloating, sensation of excess gas)
Difficulty eating, sensation of food being stuck in the stomach.
Difficulty with bowel movements (constipation or straining)
Nausea and/or vomiting
Thirst
Weakness, lack of energy, fatigue, difficulty moving.

How Gastroparesis Acts in The Body. Source:https://www.pinterest.com/pin/278026976974184742/?lp=true









Secondary Outcome Measures:

Improvement in gastroparesis symptoms [ Time Frame: Baseline, 2, 4 and 6 weeks ]
Change in weight compared to baseline

Improvement in gastroparesis symptoms [ Time Frame: Baseline, 2, 4 and 6 weeks ]

Changes in the Gastroparesis Cardinal Symptom Index (GCSI) daily diary as compared to baseline. This is a six point severity scale (0-5 with 0= none and 5 = very severe) that rates the following symptoms
Nausea
Early satiety
Postprandial fullness
Bloating
Upper abdominal pain
Retching
Vomiting
Stomach fullness
Loss of appetite
Stomach or belly visibly large



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study: 16 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: Female or male
Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

Patients with gastroparesis confirmed with symptoms and a gastric emptying study.
Inability to maintain adequate caloric intake by standard dietary measures for gastroparesis due to gastrointestinal symptoms

Exclusion Criteria:

Recent diagnosis of disorder other than gastroparesis that could affect food intake
Oropharyngeal dysphagia or other condition with risk for aspiration from oral ingestion.
Allergic reactions to any of the ingredients of the nutritional drink
Current pregnancy. Pregnancy status will be determined by questioning the potential subject.
Patient with gastrostomy/jejunostomy tube feeds or on total parenteral nutrition
Currently taking any anti-coagulant


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03500354

Contacts

Contact: Pankaj J Pasricha, MD 4105027173 ppasric1@jhmi.edu
Contact: Carmen Roberts 4105027173 ccroberts@jhmi.edu

Locations

United States, Maryland
Johns Hopkins University Active, not recruiting
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
Investigators

Principal Investigator: Pankaj J Pasricha, MD Johns Hopkins University
More Information
Go to


Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03500354 History of Changes
Other Study ID Numbers: IRB00157677
First Posted: April 17, 2018 Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No


Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johns Hopkins University:

malnutrition


Additional relevant MeSH terms:

Gastroparesis
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Paralysis
Neurologic Manifestations
Signs and Symptoms"

Source:https://preferredresearchpartners.com/gastroparesis-infographic/

Velusetrag and Investigational Medicine Trials for Gastrointestinal Motility Disorders

One of my Gastroparesis friends brought this medication to my attention this morning. A special thanks to Robin for kping me informed about these trials.

Some of these trials were done a year ago, while some of these are up to date. I wanted to include them all so that the progression of these clinical trials can be seen. It gives me hope that there are clinical trials being conducted to help find a less invasive way to help motility in those who have Gastroparesis.



According to Theravance Biopharma,

"Velusetrag is an oral, investigational medicine developed for gastrointestinal motility disorders. It is a highly selective agonist with high intrinsic activity at the human 5-HT4 receptor and is being developed in collaboration with Alfa Wassermann in a Phase 2 program to test its efficacy, safety and tolerability in the treatment of patients with gastroparesis. A Phase 2b study is currently underway following positive top-line results from a Phase 2 proof-of-concept trial.


Axelopran (TD-1211) is a once-daily, oral peripherally active mu opioid receptor antagonist being developed for the treatment of opioid induced constipation (OIC). Axelopran, which has completed long term toxicology studies, is intended to normalize bowel function without impacting analgesia. As a stand-alone treatment, Axelopran has been successfully advanced through Phase 2 studies, demonstrating a rapid restoration of normal bowel function followed by maintenance in OIC patients compared to placebo. Phase 2 study data also shows statistically significant improvements in a range of gastrointestinal symptoms in OIC patients for Axelopran as compared to placebo. We are refining the development and commercial strategy for both single agent and a fixed-dose combination of Axelopran, as well as speaking with potential collaborators.

We believe that pairing Axelopran and an opioid in a fixed-dose combination (FDC) could present an important market opportunity, as it has the potential to provide pain relief without constipation in a single abuse-deterrent pill for patients using opioids on a chronic basis. To this end, we have developed a proprietary spray-coating technology and applied it to the creation of a FDC of Axelopran and controlled-release Oxycodone.

To date, we have successfully conducted a Phase 1 study of our novel Axelopran FDC, showing that our proprietary spray-coating formulation allowed Oxycodone to be coated with Axelopran in a single pill without any modification of oxycodone, its activity or abuse-deterrent characteristics. Based on our work to date, we believe our spray-coating technology is applicable to a broad range of opioids, allowing for a potential FDC platform. We are refining the development and commercial strategy for both single agent and a FDC of Axelopran, as well as speaking with potential collaborators.



TD-8954 is a selective 5-HT4 receptor agonist being investigated for potential use in the treatment of gastrointestinal motility disorders, including enteral feeding intolerance ("EFI"). Millennium Pharmaceuticals, Inc., a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited has a global license, development and commercialization agreement for TD-8954 for potential use in the treatment of gastrointestinal motility disorders, including short-term intravenous use for EFI to achieve early nutritional adequacy in critically ill patients at high nutritional risk, for which TD-8954 received U.S. Food and Drug Administration (FDA) Fast Track Designation.



TD-1473 is an intestinally restricted pan-janus kinase (JAK) inhibitor that has demonstrated a high affinity for each of the JAK family of enzymes (JAK1, JAK2, JAK3 and TYK2). Through the inhibition of these enzymes, TD-1473 interferes with the JAK/STAT signaling pathway and, in turn, modulates the activity of a wide range of pro-inflammatory cytokines. Importantly, as an intestinally restricted treatment, TD-1473 is specifically designed to distribute adequately and exclusively to the tissues of the intestinal tract and to minimize systemic exposure. As such, we believe that this novel approach to JAK inhibition has the potential to treat inflammation in the tissues of the intestinal tract while minimizing the risk of systemic side effects. We are conducting a Phase 1 clinical study of TD-1473."

Image Source: Located on the image.





According to Government Clinical Trials,

"Brief Summary:

This is a multicenter, randomized, double-blind, incomplete block, three period fixed sequence crossover, multicenter, placebo-controlled study. The study will assess three oral doses of velusetrag (5 mg, 15 mg, and/or 30 mg) or placebo, administered once daily in three periods of 1-week duration each, with a 1-week washout period between treatment periods, in subjects with diabetic or idiopathic gastroparesis.

Study 0093 will evaluate the effect of Velusetrag in subjects with diabetic or idiopathic gastroparesis by assessing changes in gastric emptying.

Velusetrag (INN,[1] USAN; previously known as TD-5108) is an experimental drug candidate for the treatment of gastric neuromuscular disorders including gastroparesis, and lower gastrointestinal motility disorders including chronic idiopathic constipation and irritable bowel syndrome.[2] It is a potent, selective, high efficacy 5-HT4 receptor serotonin agonist [3] being developed by Theravance Biopharma[4] and Alfa Wassermann.[5] Velusetrag demonstrates less selectivity for other serotonin receptors, such as 5-HT2 and 5-HT3, to earlier generation 5-HT agonists like cisapride[6] and tegaserod.[7]

In a large clinical trial in patients with chronic idiopathic constipation (n=401), velusetrag statistically and clinically improved the frequency and consistency of complete spontaneous bowel movements (CSBMs) compared to placebo. Doses of 15 and 30 mg were well tolerated compared to placebo.[8]

Velusetrag showed accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing in healthy volunteer subjects.[9] In addition, velusetrag showed accelerated gastric emptying in patients with diabetic or idiopathic gastroparesis. The proportion of patients who experienced at least a 20% improvement is gastric emptying ranged from 20% to 52% for velusetrag dosed patients and 5% for placebo patients.[10][11]

On December 6, 2016, Theravance Biopharma announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to velusetrag for the treatment of symptoms associated with diabetic and idiopathic Gastroparesis.[12]

As of May 10, 2017, Velusetrag is being studied, at doses of 5, 15 and 30 mg over a 12 week treatment period, for symptomatic improvement in patients with diabetic or idiopathic gastroparesis in the DIGEST study.[13]"

References
"WHO Drug Information, Vol. 24, No. 1, 2010. International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 63" (PDF). World Health Organization. p. 79. Retrieved 26 April 2016.
M. Vazquez-Roque, and M. Camilleri (2011). "Velusetrag". Drugs of the Future. 36 (6): 447–454. doi:10.1358/dof.2011.036.06.1594078.
Smith, JA; Beattie, DT; Marquess, D; Shaw, JP; Vickery, RG; Humphrey, PP (2008). "The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity". Naunyn-Schmiedeberg's archives of pharmacology. 378 (1): 125–37. doi:10.1007/s00210-008-0282-y. PMID 18415081.
"Theravance Biopharma: Programs". Theravance Biopharma. Retrieved 2017-05-10.
"Theravance and Alfa Wassermann Enter Into Agreement to Develop and Commercialize Velusetrag for Gastroparesis". www.sec.gov. Retrieved 2017-05-10.
"Cisapride". Wikipedia. 2017-02-17.
"Tegaserod". Wikipedia. 2017-02-17.
Goldberg, M; Li, YP; Johanson, JF; Mangel, AW; Kitt, M; Beattie, DT; Kersey, K; Daniels, O (2010). "Clinical trial: The efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation - a 4-week, randomized, double-blind, placebo-controlled, dose-response study". Alimentary pharmacology & therapeutics. 32 (9): 1102–12. doi:10.1111/j.1365-2036.2010.04456.x. PMID 21039672.
Manini, ML; Camilleri, M; Goldberg, M; Sweetser, S; McKinzie, S; Burton, D; Wong, S; Kitt, MM; et al. (2010). "Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation". Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. 22 (1): 42–9, e7–8. doi:10.1111/j.1365-2982.2009.01378.x. PMC 2905526 Freely accessible. PMID 19691492.
"Theravance Biopharma Presents Positive Phase 2 Study Data on Velusetrag (TD-5108) for Treatment of Gastroparesis in "Poster of Distinction" at Digestive Disease Week (DDW) 2015 (NASDAQ:TBPH)". investor.theravance.com. Retrieved 2017-05-10.
House, SA Editor Douglas W. (2015-05-18). "Theravance's velusetrag performs well in gastroparesis study". Seeking Alpha. Retrieved 2017-05-10.
Morales, Sysy (2016-12-18). "FDA Gives Fast Track Designation for Gastroparesis Treatment". Diabetes Daily. Retrieved 2017-05-10.
"The Diabetic and Idiopathic Gastroparesis Efficacy, Safety, and Tolerability (DIGEST) Study". ClinicalTrials.gov. Retrieved 26 April 2016.





As of right now, these are the only options available to people battling Gastroparesis:

Source: Located on image.




According to the U.S. Library of National Medicine,

"Velusetrag has been used in trials studying the treatment of Gastroparesis and Alzheimer's Disease. It is a highly selective serotonin receptor agonist effective in patients with chronic constipation. It is being developed by Theravance. Velusetrag was discovered by Theravance through the application of its multivalent drug design in a research program dedicated to finding new treatments for GI motility disorders."

Source: unknown.



As of August of 2017, According to Theravance Biopharma,

"Theravance Biopharma Announces Positive Top-Line Results from Phase 2b Study of Velusetrag (TD-5108) in Patients with Gastroparesis: Improvements in Symptoms and Normalized Gastric Emptying Demonstrated in both Diabetic and Idiopathic Gastroparesis Patients



Theravance Biopharma, Inc.
Aug 02, 2017, 07:00 ET


DUBLIN, Ireland, Aug. 2, 2017 /PRNewswire/ -- Theravance Biopharma, Inc. (NASDAQ: TBPH) ('Theravance Biopharma' or the 'Company') today announced positive results from a 12-week, Phase 2b study of velusetrag (TD-5108), an oral investigational drug in development for the treatment of patients with diabetic and idiopathic gastroparesis. Top-line results from the study demonstrated statistically significant improvements in gastroparesis symptoms and gastric emptying in patients receiving 5 mg of velusetrag as compared to placebo. Additionally, velusetrag was shown to be generally well-tolerated, with 5 mg and placebo having comparable rates of adverse events (AEs) and serious adverse events (SAEs).

The study was conducted in 232 patients with either diabetic or idiopathic gastroparesis who received either velusetrag (5, 15 or 30 mg) or placebo, administered orally as a once daily dose. After four weeks of dosing, when the primary assessments were made, patients in the 5 mg velusetrag treatment arm demonstrated statistically significant improvements in symptom scores compared to placebo in two separate patient reported outcome (PRO) tools: the Gastroparesis Cardinal Symptom Index (GCSI) (nominal p = 0.0327) and the Gastroparesis Rating Scale (GRS) (nominal p = 0.0159). Improvements in GRS total score were maintained at 12 weeks of treatment (nominal p = 0.0427). Compared to placebo, patients in the 5 mg treatment arm also demonstrated statistically significant improvements in gastric emptying time (nominal p < 0.001) and in individual disease-specific symptom scores including post-prandial fullness/early satiety, bloating and upper abdominal pain (all nominal p < 0.05). Importantly, the symptom improvements seen with 5 mg of velusetrag were observed in both diabetic and idiopathic gastroparesis patients. The primary endpoint analysis included a pre-specified analysis of each dose against placebo to report nominal p-values. The analysis also included multiplicity adjustments of p-values to account for three dose comparisons to placebo. Patients in the 15 and 30 mg velusetrag study arms did not demonstrate nominally statistically significant improvements in gastroparesis symptoms versus placebo, possibly due to an increased frequency in gastrointestinal side effects at these doses that may have been caused by rapid emptying of the stomach. The lack of dose response resulted in a lack of statistical significance across the three doses when adjusted for multiplicity. As a result, the statistical comparisons for the 5 mg dose are not adjusted for multiple comparisons, and all are quoted as nominal. Of note, the 15 mg and 30 mg doses remained highly statistically significant compared to placebo in gastric emptying time (nominal p < 0.001), as measured by scintigraphy. "We are very encouraged by the results of this study as they demonstrate not only consistent evidence of improved gastric emptying but also meaningful improvement in gastroparesis symptoms following treatment with 5 mg of velusetrag. The findings from this study demonstrate that a 5 mg dose was sufficient to ameliorate the symptoms of gastroparesis. We believe that these findings provide clear evidence of the potential benefit of velusetrag in patients with gastroparesis, a debilitating disease in significant need of therapeutic innovation," said Brett Haumann, MD, Chief Medical Officer of Theravance Biopharma. "We are now preparing to meet with regulators to discuss the next phase in our development plan." Velusetrag was shown to be generally well-tolerated, with rates of AEs and SAEs comparable between the 5 mg dose and placebo. The most commonly reported AEs across all groups (active treatment and placebo) were diarrhea, nausea and headache. Consistent with velusetrag's mechanism of action, patients receiving treatment demonstrated higher rates of diarrhea and nausea/vomiting than those receiving placebo, and these rates were numerically highest in the 15 and 30 mg arms of the study. Diabetic subjects treated with velusetrag generally maintained adequate glucose control throughout the study, and there were no episodes of hyperglycemia reported. There was no difference in the number of cardiac adverse events, with four events reported in placebo subjects and four events reported in all velusetrag treated subjects. There were no deaths reported in the study. Theravance Biopharma intends to present additional results from the study at upcoming medical conferences, as well as in appropriate scientific journals. Theravance Biopharma will hold a conference call and webcast presentation today at 8:00 am ET to discuss the results of the Phase 2b study of velusetrag. To participate in the live call by telephone, please dial (855) 296-9648 from the U.S., or (920) 663-6266 for international callers, using the confirmation code 61886684. To listen to the conference call live via the internet please visit Theravance Biopharma's website at www.theravance.com, under the Investor Relations section, Presentations and Events. To listen to the live call please go to Theravance Biopharma's website 15 minutes prior to its start to register, download, and install any necessary audio software. A replay of the conference call will be available on Theravance Biopharma's website through September 2, 2017. An audio replay will also be available through 8:00 am ET on August 9, 2017 by dialing (855) 859-2056 from the U.S., or (404) 537-3406 for international callers, using the confirmation code 61886684. [**Blogger's NOTE: Call has already been done as of today] About the Phase 2b Study

The study was a multicenter, double-blind, placebo-controlled, parallel group Phase 2b characterizing the impact on symptoms and gastric emptying of multiple doses of velusetrag administered once daily over 12 weeks of therapy. The study enrolled 232 subjects with diabetic or idiopathic gastroparesis with documented gastric delay, by either gastric emptying scintigraphy (GES) or gastric emptying breath test (GEBT), and documented symptoms prior to and throughout the baseline period. Two daily patient reported outcomes (PRO) tools were used to characterize symptom change: the Gastroparesis Cardinal Symptom Index (GCSI), which assessed the severity of three cardinal symptom domains; and the Gastroparesis Rating Scale (GRS), which assessed severity, frequency and timing of seven symptom domains, including the three symptom domains in the GCSI. GRS is a proprietary PRO tool being developed by the Company with academic collaboration. The primary endpoint in the study was mean GCSI score at the end of week 4 of the treatment period.


About Gastroparesis

Gastroparesis is a disorder characterized by delayed gastric emptying and symptoms of gastric retention in the absence of mechanical obstruction. In the United States, it is estimated to affect approximately six million individuals, or 1.8% of the population, and includes two major sub-classes: those with diabetic gastroparesis (29% of the overall gastroparesis population) and those with idiopathic gastroparesis (36%).1 Symptoms of gastroparesis are variable but typically include nausea, vomiting, early satiety, postprandial bloating/fullness or upper abdominal discomfort. Severe cases may also suffer from dehydration, electrolyte disturbances, weight loss and malnutrition. There is also a correlation between severity of symptoms and impairment of quality of life.2


About Velusetrag

Velusetrag is an oral, once-daily investigational medicine discovered internally and developed for gastrointestinal motility disorders. The compound has been granted Fast Track designation by the U.S Food and Drug Administration (FDA) for the treatment of symptoms associated with idiopathic and diabetic gastroparesis.

Velusetrag is a highly selective agonist with high intrinsic activity at the human 5-HT4 receptor. 5-hydroxytryptamine receptor 4 (5-HT4) agonists are established as gastrointestinal (GI) prokinetic agents for the treatment of GI tract dysfunction, such as chronic constipation. Velusetrag (or TD-5108) is a 5-HT4 receptor agonist that demonstrates high in vitro intrinsic activity and selectivity for the 5-HT4 receptor and has no significant affinity for all other receptor types, ion channels, or enzymes tested.

A previous Phase 2 trial of velusetrag showed that all three doses of velusetrag (5, 15 and 30 mg) reduced gastric emptying time (GE t1/2) compared to placebo in patients with either diabetic or idiopathic gastroparesis. The completed Phase 2 trial was the first study to evaluate gastric emptying, a diagnostic criterion for gastroparesis, in a patient population including both diabetic and idiopathic gastroparesis patients, as opposed to diabetic gastroparesis patients only. In addition, velusetrag has completed a 400-patient Phase 2 proof-of-concept study in chronic idiopathic constipation, demonstrating statistically significant prokinetic activity at all three doses tested in that study.

Velusetrag is being developed by Theravance Biopharma in collaboration with Alfasigma (S.p.A.) ("Alfasigma"). Under the terms of the agreement, Alfasigma has an exclusive option to develop and commercialize velusetrag in the European Union, Russia, China, Mexico and certain other countries, while Theravance Biopharma retains full rights to velusetrag in the United States, Canada, Japan and certain other countries.


About Theravance Biopharma

Theravance Biopharma is a diversified biopharmaceutical company with the core purpose of creating medicines that make a difference in the lives of patients suffering from serious illness.

Our pipeline of internally discovered product candidates includes potential best-in-class medicines to address the unmet needs of patients being treated for serious conditions primarily in the acute care setting. VIBATIV® (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the U.S., Europe and certain other countries for certain difficult-to-treat infections. Revefenacin (TD-4208) is a long-acting muscarinic antagonist (LAMA) being developed as a potential once-daily, nebulized treatment for chronic obstructive pulmonary disease (COPD). Our neprilysin (NEP) inhibitor program is designed to develop selective NEP inhibitors for the treatment of a range of major cardiovascular and renal diseases, including acute and chronic heart failure, hypertension and chronic kidney diseases, such as diabetic nephropathy. Our research efforts are focused in the areas of inflammation and immunology, with the goal of designing medicines that provide targeted drug delivery to tissues in the lung and intestinal tract in order to maximize patient benefit and minimize risk. The first program to emerge from this research is designed to develop intestinally restricted pan-Janus kinase (JAK) inhibitors for the treatment of a range of inflammatory intestinal diseases.

In addition, we have an economic interest in future payments that may be made by Glaxo Group Limited or one of its affiliates (GSK) pursuant to its agreements with Innoviva, Inc. relating to certain drug development programs, including the Closed Triple (the combination of fluticasone furoate, umeclidinium, and vilanterol), currently in development for the treatment of COPD and asthma.

For more information, please visit www.theravance.com.


THERAVANCE®, the Cross/Star logo, and VIBATIV® are registered trademarks of the Theravance Biopharma group of companies. Trademarks, trade names or service marks of other companies appearing on this press release are the property of their respective owners.

This press release and the conference call will contain contains certain 'forward-looking' statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives, expectations and future events. Theravance Biopharma intends such forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Examples of such statements include statements relating to: the company's strategies, plans and objectives, the company's regulatory strategies and timing of clinical studies, the potential benefits and mechanisms of action of the company's product and product candidates, the company's expectations for product candidates through development, potential regulatory approval and commercialization (including their potential as components of combination therapies) and the company's expectations for product sales. These statements are based on the current estimates and assumptions of the management of Theravance Biopharma as of the date of the press release and are subject to risks, uncertainties, changes in circumstances, assumptions and other factors that may cause the actual results of Theravance Biopharma to be materially different from those reflected in the forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, among others, risks related to: delays or difficulties in commencing or completing clinical studies, the potential that results from clinical or non-clinical studies indicate the company's product candidates are unsafe or ineffective (including when our product candidates are studied in combination with other compounds),the feasibility of undertaking future clinical trials for our product candidates based on FDA policies and feedback, dependence on third parties to conduct clinical studies, delays or failure to achieve and maintain regulatory approvals for product candidates, risks of collaborating with or relying on third parties to discover, develop and commercialize product and product candidates, and risks associated with establishing and maintaining sales, marketing and distribution capabilities with appropriate technical expertise and supporting infrastructure. Other risks affecting Theravance Biopharma are described under the heading 'Risk Factors' contained in Theravance Biopharma's Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 9, 2017 and Theravance Biopharma's other filings with the SEC. In addition to the risks described above and in Theravance Biopharma's filings with the SEC, other unknown or unpredictable factors also could affect Theravance Biopharma's results. No forward-looking statements can be guaranteed and actual results may differ materially from such statements. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Theravance Biopharma assumes no obligation to update its forward-looking statements on account of new information, future events or otherwise, except as required by law.

References:

1 American Gastroenterological Association. "Technical Review on the Diagnosis and Treatment of Gastroparesis." http://www.gastrojournal.org/article/S0016-5085(04)01634-8/fulltext. Published online July 27, 2005.

2 Journal of Neurogastroenterology and Motility. "Prevalence of Hidden Gastroparesis in the Community: The Gastroparesis 'Iceberg'." http://www.jnmjournal.org/journal/view.html?doi=10.5056/jnm.2012.18.1.34. Published online January 16, 2012."

In conclusion, these trials look promising. Hopefully, soon, we will have more treatments for Gastroparesis. There are several clinical trials being conducted that show promising results. I have more clinical trials in another blog article I wrote, which you can find here: http://www.emilysstomach.com/2018/06/fda-accepts-cardiac-safety-trial-for.html. I really hope that these trials continue to show promise, because as of right now, there are medications that can cause permanent neurological side effects, or very extreme measures like stomach surgery or the gastric pacemaker to help with Gastroparesis. We need something less invasive that will help to increase our motility. My friend Paul recommended this article: https://coatings.specialchem.com/tech-library/article/hsp-science-based-formulation-for-coatings for more information. He says,"After a week of research I have put together comprehensive article on "'HSP for Coatings.'" It's pwtj ceckok -

Clinical Trial to Test Efficiency of IV Hemin for Gastroparesis

Clinical Trial to Test Efficiency of IV Hemin for Gastroparesis

Gastroparesis is a syndrome marked by slow gastric emptying and symptoms such as nausea, vomiting, bloating, early fullness and abdominal pain. Although long associated with type 1 diabetes and now, increasingly, with type 2, the cause in many cases remains unknown.

But gastroenterologist Gianrico Farrugia, M.D., stresses that in the last few years, scientists at Mayo Clinic and elsewhere have made marked progress in understanding the pathological mechanisms underlying the disorder. Much of the current research focuses on the interstitial cells of Cajal (ICC), which are needed for normal stomach emptying.

"The ICC act as intestinal pacemakers for smooth muscle function," he says. ''They also amplify neuronal signals, act as mechanosensors and set the smooth muscle membrane potential gradient. Both human and animal models demonstrate loss of these cells in diabetic and idiopathic gastroparesis."

Normal gut function requires a balance between processes that injure ICC and processes that generate and maintain them. In people with diabetic gastroparesis, the balance shifts toward factors that damage ICC, including relative insulinopenia and deficiency of insulin-like growth factor-1 (IGF-1), both of which can cause smooth muscle atrophy.

Dr. Farrugia says a critical factor is oxidative stress resulting from low levels of heme oxygenase-1 (HO-1), an important protector against oxidative injury.

"When the mechanisms that normally counteract oxidative stress are impaired, especially upregulation of heme oxygenase-1, ICC are lost and gastric emptying is delayed. In mouse models, restoring HO-1 prevents and even reverses these cellular changes and restores normal gastric function."
Macrophage switching

In the stomach wall, HO-1 expression occurs in a particular subset of macrophages — CD206-positive M2 macrophages — whose cytoprotective effect on ICC appears related to the production of small amounts of carbon monoxide.

Dr. Farrugia says, "When the upregulation of HO-1 is lost, M2 macrophages are replaced by proinflammatory M1 macrophages. These cells, which do not produce carbon monoxide, are associated with ICC damage and the development of delayed stomach emptying. Thus, the upregulation of HO-1 in M2 macrophages seems critical to the prevention of diabetes-related gastroparesis."
Clinical trials

In mouse studies, hemin, a biological product of red blood cells, has been shown to boost the production of HO-1, thereby reducing oxidative stress, allowing repair of the ICC network and normalizing gastric function. Now, Dr. Farrugia and colleague Adil E. Bharucha, MBBS, M.D., are recruiting patients for the first randomized controlled clinical trial to determine whether intravenous hemin therapy is equally beneficial for people with gastroparesis.

"The hope is that this clinical trial may lead to an effective medication for gastroparesis — one that doesn't just manage symptoms as prokinetics do, but that actually targets the cause of the disease."

The need for better treatments is especially critical now, Dr. Farrugia says, because the incidence of gastroparesis is increasing. The number of hospitalizations for the disorder grew by nearly 158 percent from 1995 to 2004. "The vast majority of patients are young women of childbearing age. This disease causes tremendous disruption in patients' lives and in the lives of their families, and none of the treatments we have are ideal."


Link to the article can be found HERE.