Last updated: 11/07/2018 03:58:38
The effect of single doses of the motilin receptor agonist GSK962040 in Type I Diabetic patients with gastroparesis
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Multicenter, Double-Blind, Randomized Placebo-Controlled Phase II Study to Evaluate the Pharmacodynamics, Safety, Tolerability, and PK of Single Doses of the Oral Motilin Receptor Agonist GSK962040, in Type 1 Diabetic Male and Female Patients with Gastroparesis
Trial description: The purpose of this study is to assess the pharmacodynamic effects (gastric emptying), safety, tolerability, and pharmacokinetics of single doses of GSK962040 in Type 1 diabetic patients with gastroparesis.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Gastric emptying, as measured by the 13C octanoic acid breath test: Gastric half emptying time (t1/2b) and duration of the lag time (tlag)
Timeframe: Day 1 (1.5 h post-dose to 5.5 h post-dose)
Gastric emptying, as measured by the 13C octanoic acid breath test: Gastric evacuation coefficient (GEC)
Timeframe: Day 1 (1.5 h post-dose to 5.5 h post-dose)
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timeframe: Up to Follow-up (10-14 days post last dose)
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Baseline (Day 1 pre-dose) to Day 1 (2 h post-dose)
Change from Baseline in heart rate
Timeframe: Baseline (Day 1 pre-dose) to Day 1 (2 h post-dose)
Change from Baseline in electrocardiography (ECG) parameters
Timeframe: Baseline (Day 1 pre-dose) to Day 1 (2 h post-dose)
Number of participants outside the range of potential clinical importance for SBP, DBP and heart rate
Timeframe: Baseline (Day 1 pre-dose) to Day 1 (2 h post-dose)
Number of participants with abnormal 12-lead ECG findings
Timeframe: 24 h post-dose
Change from Baseline in clinical chemistry: alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT)
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in clinical chemistry: direct bilirubin, total bilirubin, creatinine
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in clinical chemistry: chloride, glucose, potassium, sodium, urea/blood urea nitrogen (BUN)
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in hematology parameters: basophils, eosinophils, lymphocytes, monocytes, total neutrophils (Total ANC - total absolute neutrophil count), platelet count, white blood cell (WBC) count
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in hematology parameters: hematocrit
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in hematology parameters: Mean Corpuscle Hemoglobin
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in hematology parameters: hemoglobin, mean corpuscle hemoglobin concentration (MCHC)
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in hematology parameters: mean corpuscle volume
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Change from Baseline in hematology parameters: red blood cell (RBC) count
Timeframe: Baseline (Day -1) to Day 1 (24 h post-dose)
Pharmacokinetic (PK) parameters of GSK962040: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from time zero (pre-dose) extrapolated to infinite time (AUC(0-inf))
Timeframe: Day 1 (pre-dose, 0.25 h to 24 h post-dose)
PK parameters of GSK962040: maximum observed concentration (Cmax) for single-dose
Timeframe: Day 1 (pre-dose, 0.25 h to 24 h post-dose)
PK parameters of GSK962040: time of occurrence of Cmax (Tmax) for single-dose
Timeframe: Day (pre-dose, 0.25 h to 24 h post-dose)
PK parameters of GSK962040: Apparent clearance following oral dosing (CL/F)
Timeframe: Day 1 (pre-dose, 0.25 h to 24 h post-dose)
PK parameters of GSK962040: Apparent volume of distribution after oral administration (V/F)
Timeframe: Day 1 (pre-dose, 0.25 h to 24 h post-dose)
PK parameters of GSK962040: half-life (T1/2)
Timeframe: Day 1 (pre-dose, 0.25 h to 24 h post-dose)
Secondary outcomes:
Bowel movement parameters: Time to first bowel movement after first dose
Timeframe: Day 1 (24 h post-dose)
Bowel movement parameters: Bowel movement count
Timeframe: Day -1, pre-treatment, Day 1 (24 h post-dose)
Bowel movement parameters: Stool consistency (Bristol Stool Form scale)
Timeframe: Day -1, pre-treatment, Day 1 (24 h post-dose)
PK/Pharmacodynamic (PD) relationship of Pancreatic polypeptide (PP), Glucagon-Like Peptide-1 (GLP-1), and ghrelin after a single dose of GSK962040
Timeframe: Predose and Day 1 (0 to 2 h post-dose)
Mean Plasma glucose concentration at 1.5, 2, 3, 4, 5.5 and 6h post-dose
Timeframe: Day -1, pre-dose, 0.25 h, 0.5h, 0.75 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5.5 h and 6 h post-dose
Daily energy intake as a measure of food intake
Timeframe: Up to 24 hours post-dose
Interventions:
Drug: GSK962040 25 mg
Drug: Placebo
Drug: GSK962040 50 mg
Drug: GSK962040 1250 mg
Enrollment:
10
Observational study model:
Not applicable
Primary completion date:
2010-19-11
Time perspective:
Not applicable
Clinical publications:
Hellstrom PM, Tack J, Vasist LV, Hacquoil K, Barton ME, Richards DB, Alpers DH, Sanger GJ, Dukes GE. The Pharmacodynamics, Safety, and Pharmacokinetics of Single Doses of the Motilin Agonist, Camicinal, in Type 1 Diabetes Mellitus with Slow Gastric Emptying. Br J Pharmacol. 2016;173(11):1768-1777
Medical condition
Gastroparesis
Product
camicinal
Collaborators
Not applicable
Study date(s)
June 2009 to November 2010
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 70 years
Accepts healthy volunteers
No
- Controlled Type 1 Diabetes Mellitus (glucose < 250 mg/dL) with onset < 30 years of age.
- Male or female between 18 and 70 years of age, inclusive.
- Patient has acute severe gastroenteritis
- Patient has a gastric pacemaker
Inclusion and exclusion criteria
Inclusion criteria:
- Controlled Type 1 Diabetes Mellitus (glucose < 250 mg/dL) with onset < 30 years of age.
- Male or female between 18 and 70 years of age, inclusive.
- Patient has documented diagnosis of moderate to severe gastroparesis (> 30% at 2 h as determined by scintigraphy; or t1/2b > 109 min as determined by 13C-octanoic acid breath test). All of the following apply:
- Confirmed delayed gastric emptying (properly conducted gastric emptying assessments within last 6 months acceptable) AND a minimum 3 month history of relevant symptoms for gastroparesis (e.g., chronic postprandial fullness, postprandial nausea, vomiting)
- A female patient is eligible to participate if she is of:
- Non-childbearing potential
- Child-bearing potential and agrees to use contraception for at least 4 days following the last dose of study medication.
- Male patients must agree to use contraception from the time of the first dose of study medication through at least 4 days after the last dose of study medication.
- Body weight ≤110 kg and BMI < 32.0 kg/m2 (inclusive).
- Patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction within the previous 12 months
- Dosage of any concomitant medications has been stable for at least 3 weeks, except for routine adjustments in daily insulin treatments
- HbA1c level is ≤ 10.0%
- Calculated creatinine clearance > or equal to 50 ml/min
- QTcB or QTcF < 450 msec or QTc<480msec in patients with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period.
- AST, ALT, 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 parenteral feeding
- Patient has daily persistent severe vomiting
- Patient has pronounced dehydration
- Patient has had clinical diabetic ketoacidosis in last 4 weeks
- Patient has a history of eating disorders (anorexia nervosa, binge eating, bulimia)
- Use of medications potentially influencing upper gastrointestinal motility or appetite within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin))
- Patient is taking opiates.
- Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to the first dose of study medication.
- History or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
- Presence of thyroid dysfunction (NOTE: patients with abnormal TSH at screening/baseline are not eligible. Patients with a history of hypothyroidism on a stable dose of thyroid replacement therapy are eligible to participate in the study).
- The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- 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 GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Pregnant females as determined by positive serum or urine hCG test (from the first urine of the day) at screening or prior to dosing.
- Lactating or pregnant females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Patients deemed unable to comply with the procedures outlined in the protocol may be excluded at the Investigator’s discretion.
- For male volunteers: An unwillingness of the male patient to comply with the contraception requirements listed in Section 8.1, from the time of the first dose of study medication until at least 4 days following administration of the last dose of study medication.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2010-19-11
Actual study completion date
2010-19-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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