A Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate the Effect of 12 Weeks of Once-daily Dosing of the Oral Motilin Receptor Agonist Camicinal, on Gastroparesis Symptoms in Type 1 and 2 Diabetic Subjects With Gastroparesis
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Gastroparesis
- Sponsor
- GlaxoSmithKline
- Enrollment
- 114
- Locations
- 1
- Primary Endpoint
- Percentage of Responders Based on the Fullness/Early Satiety Subscale (Responders) as Assessed by Gastrointestinal Cardinal Symptom Index-Daily Diary (GCSI-DD) at Week 12
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study is a randomized, double-blind, placebo controlled trial designed to confirm the symptomatic effects of camicinal treatment vs. placebo, on gastroparesis symptoms in type 1 and 2 diabetic subjects with gastroparesis. The primary purpose of this study is to determine if a low-dose of camicinal (25 milligram[mg]) for 12 weeks of repeat administration improves gastroparesis symptoms as measured by the Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) in approximately 120 subjects with type 1 or 2 diabetes mellitus (DM) who have documented abnormally slow gastric emptying and have symptoms consistent with gastroparesis.
Subjects will be randomized in a 1:1 ratio to receive either camicinal or placebo. The study will consist of a screening/baseline period of up to 35 days, a 12 week treatment period, a 2-week post-treatment assessment of symptoms and a 14 day (+/- 2 days) post treatment safety follow-up visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Type 1 or 2 diabetes mellitus (acetylated hemoglobin A1 \[HbA1c\] \<=11.0%)
- •Male or female between 18 and 80 years of age, inclusive.
- •Patient has gastroparesis at screening. A patient is eligible if one of the following criteria are met: Gastric half-time of emptying \>upper limit of normal as determined by Carbon-13 radioisotope (C13) oral breath test; % C13-dose recovered \< lower limit of normal at 90 or 120 minutes
- •Patient must report a \>=3 month history of relevant symptoms of gastroparesis (e.g., chronic post-prandial fullness, early satiety, post-prandial nausea).
- •Patients will have a mean of the daily scores over a minimum of 7 days indicating \>= mild (2) severity for the fullness/early satiety subscale as assessed using the GCSI-DD during the screening period prior to randomization.
- •A female patient is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] \>40 milli international units per milliliter \[mIU/mL\], or a value consistent with the local laboratory standard value, is confirmatory) or is of child-bearing potential and agrees to use contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female patients must agree to use contraception for at least 5 days following the last dose of study medication.
- •Body mass index (BMI) \>18 and \<=42.0 kilogram per meter square (kg/m\^2) (inclusive).
- •QTc \<450 millisecond (msec) or QTc \<480 msec in patients with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period. The QT correction formula (Bazett's, Fridericia's, etc) used to determine inclusion and discontinuation should be the same throughout the study.
- •Aspartate aminotransferase and alanine aminotransferase \<2x upper limit of normal (ULN); alkaline phosphatase and bilirubin \<=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Exclusion Criteria
- •Patient has acute severe gastroenteritis
- •Patient has a gastric pacemaker
- •Patient is on chronic enteral (e.g., feeding tube) or parenteral feeding
- •Recent (last 6 weeks) history of poor control of diabetes e.g. hypoglycaemia requiring medical intervention, diabetic ketoacidosis, admission for control of diabetes or complications of diabetes
- •Patient has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months)
- •Patient has a history of eating disorders (anorexia nervosa, binge eating, bulimia)
- •Use of medications potentially influencing upper gastrointestinal motility or appetite at least 1 week prior to screening (e.g., prokinetic drugs, macrolide antibiotics \[erythromycin\], glucagon-like peptide-1 \[GLP-1\] mimetics)
- •Patient has had intrapyloric botox injections.
- •A patient would be eligible if the botox treatment was in the past (\>6 months previously) and was not being repeated.
- •Patient has had a gastrectomy, or major gastric surgical procedure or any evidence of bowel obstruction or strictures within the previous 12 months
Arms & Interventions
Placebo
Subjects will receive camicinal matching placebo orally once daily (QD) from Day 1 to Day 84
Intervention: Placebo
Camicinal 25mg
Subjects will receive camicinal 25 mg orally QD from Day 1 to Day 84
Intervention: Camicinal
Outcomes
Primary Outcomes
Percentage of Responders Based on the Fullness/Early Satiety Subscale (Responders) as Assessed by Gastrointestinal Cardinal Symptom Index-Daily Diary (GCSI-DD) at Week 12
Time Frame: Week 12
The GCSI-DD consists of nine symptom severity items covering the following domains: nausea/vomiting; fullness/early satiety, and bloating. In addition, the GCSI-DD contains two symptom severity items upper abdominal pain and overall rating of gastroparesis symptoms. Participants were asked to rate each symptom on a 6-point scale from 0 to 5 with lower scores representing less symptom severity and higher scores indicating more severe symptoms. Fullness/early satiety response is defined as an improvement from Baseline by at least one point in the weekly average for the subscale. A participant was defined as a responder if the participant's weekly average change from Baseline in the fullness/early satiety response score improved by at least 1 point. Percentage of participants showing response were presented.
Secondary Outcomes
- Trough Plasma Concentration of Camicinal on Day 28 and Day 84(Day 28 and Day 84)
- Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12(Baseline (Screening) and Week 12)
- Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days(Up to 100 days)
- Number of Participants With Change From Baseline (Day 1) in Heart Rate of PCI Over 100 Day(Up to 100 days)
- Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days(Up to 100 days)
- Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period(Up to 100 days)
- Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period(Up to 100 days)
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), and Adverse Events Leading to Discontinuation of the Study Drug(Up to end of follow up (100 days))