Clinical trial NCT02210000: A Study to Evaluate the Effect of Camicinal on Gastroparesis Symptoms in Type 1 and 2 Diabetic Subjects With Gastroparesis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Keywords: repeat dose
phase II
GCSI-DD
pharmacodynamics
gastroparesis
type 1 and type 2 diabetes mellitus
camicinal
GSK962040
symptoms
gut motility
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-08-06
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* Dosage of any concomitant medications has not been stable for at least 3 weeks, except for routine adjustments in daily insulin treatments.
* Estimated (or measured) glomerular filtration rate \<=30 mL/minute.
* Daily opiate use at screening
* Use of prohibited medications that potentially influence upper gastrointestinal motility or appetite, or medications that may interfere with the methods of measuring gastric emptying e.g., prokinetic drugs, macrolide antibiotics (erythromycin, azithromycin), GLP-1 mimetics, anti-cholinergics, chronic/regular use of opiates
* History or presence of clinically significant gastro-intestinal, hepatic or renal disease (including liver disease or known hepatic or biliary abnormalities, with the exception of Gilbert's syndrome or asymptomatic gallstones) or other condition that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical study.
* Concurrent enrollment in any other interventional study/(ies) involving a novel (i.e. unapproved or experimental) chemical or biopharmaceutical entity.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.
* Lactating or Pregnant females as determined by positive serum or urine human chorionic gonadotropin test (from the first urine of the day) at screening or prior to dosing.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening

Primary outcomes:
measure: 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
timeFrame: Week 12
Secondary outcomes:
measure: Change From Baseline in Individual Items, Subscales and Total Score of GCSI-DD at Week 12
timeFrame: Baseline (Screening) and Week 12
measure: Number of Participants With Change From Baseline (Day 1) in Blood Pressure of Potential Clinical Importance (PCI) Over 100 Days
timeFrame: Up to 100 days
measure: Number of Participants With Change From Baseline (Day 1) in Heart Rate of PCI Over 100 Day
timeFrame: Up to 100 days
measure: Number of Participants With Normal and Abnormal 12-lead Electrocardiogram (ECG) Measurements Over 100 Days
timeFrame: Up to 100 days
measure: Number of Participants With Change From Baseline in Hematological Abnormalities of PCI by Treatment and Visit Over Period
timeFrame: Up to 100 days
measure: Number of Participants With Change From Baseline Clinical Chemistry Abnormalities of PCI by Treatment and Visit Over Period
timeFrame: Up to 100 days
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs), and Adverse Events Leading to Discontinuation of the Study Drug
timeFrame: Up to end of follow up (100 days)
measure: Trough Plasma Concentration of Camicinal on Day 28 and Day 84
timeFrame: Day 28 and Day 84
Other outcomes:
Locations:
city: Chandler
country: United States
facility: GSK Investigational Site
state: Arizona
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Northridge
country: United States
facility: GSK Investigational Site
state: California
city: Hialeah
country: United States
facility: GSK Investigational Site
state: Florida
city: Inverness
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Port Orange
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Marietta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Towson
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Flint
country: United States
facility: GSK Investigational Site
state: Michigan
city: Wyoming
country: United States
facility: GSK Investigational Site
state: Michigan
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Poughkeepsie
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Dayton
country: United States
facility: GSK Investigational Site
state: Ohio
city: Mentor
country: United States
facility: GSK Investigational Site
state: Ohio
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Rapid City
country: United States
facility: GSK Investigational Site
state: South Dakota
city: Bristol
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Germantown
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Arlington
country: United States
facility: GSK Investigational Site
state: Texas
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Spring
country: United States
facility: GSK Investigational Site
state: Texas
city: Bountiful
country: United States
facility: GSK Investigational Site
state: Utah
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: