A Study to Evaluate the Effect of Camicinal on Gastroparesis Symptoms in Type 1 and 2 Diabetic Subjects With Gastroparesis
Condition: Gastroparesis
MeSH terms: Gastroparesis
Intervention: Placebo; Camicinal
Intervention description: Camicinal matching placebo is available as tablet to be taken orally with 100mL of water in the morning; Camicinal is available as 25 mg tablet to be taken orally with 100mL of water in the morning
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 114.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: repeat dose; phase II; GCSI-DD; pharmacodynamics; gastroparesis; type 1 and type 2 diabetes mellitus; camicinal; GSK962040; symptoms; gut motility

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