Last updated: 07/13/2021 12:40:17
Dose response of 28 days of dosing of GSK962040 in Type I and II diabetic male and female subjects with gastroparesis
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase II Study to Evaluate the Safety and Efficacy and Dose Response of 28 Days of Once-Daily Dosing of the Oral Motilin Receptor Agonist GSK962040, in Type I and II Diabetic Male and Female Subjects with Gastroparesis
Trial description: GSK962040 is a novel small molecule motilin agonist. The Phase I studies (MOT107043 and MOT109681) demonstrated that single doses of GSK962040 up to 150 mg and repeat dosing of up to 125 mg/day for 14 days were well tolerated with adverse events not occurring in greater prevalence than placebo, and no significant abnormal vital sign, ECG, or clinical laboratory findings. Pharmacokinetic parameters were linear and approximately dose proportional over the range of doses administered. Single doses of 50 mg – 150 mg GSK962040 significantly increased the rate of gastric emptying up to 40% as measured by the 13C octanoic acid stable isotope breath test. A similar effect of 50 mg and 125 mg on gastric emptying was observed throughout repeated dosing to healthy volunteers for 14-days. The aims of the present investigation (MOT114479) are to assess the pharmacodynamic effects (gastric emptying and symptoms), safety, tolerability, and pharmacokinetics of GSK962040 after 28 days of once-daily dosing in Type I and Type II diabetic subjects with gastroparesis. An additional aim is to characterize the dose/exposure – pharmacodynamic effect relationship.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Gastric half emptying time (GEt1/2)
Timeframe: Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28
Secondary outcomes:
Number of Participants with On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs)
Timeframe: Up to follow-up (5-10 days post last dose)
Change from Baseline in Systolic blood pressure (SBP) and Diastolic blood pressure(DBP) at specified time points in Semi-supine position
Timeframe: Baseline, Day 1, and Day 8
Change from Baseline in heart rate at specified time points in Semi-supine position
Timeframe: Baseline, Day 1, and Day 8
Change from Baseline in electrocardiography parameters (12-lead ECG)
Timeframe: Baseline, Day 1 and Day 28
Number of participants outside the normal range for SBP and DBP
Timeframe: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Number of participants outside the normal range for heart rate
Timeframe: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Number of participants outside the normal range for 12-lead ECG
Timeframe: Baseline (Day 1 pre-dose), Day 1, Day 14 and Day 28
Mean change from Baseline in clinical chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase
Timeframe: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Mean change from Baseline in clinical chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric acid
Timeframe: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Mean change from Baseline in clinical chemistry : Albumin, Total Protein
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Mean change from Baseline in clinical chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon dioxide content/Bicarbonate
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Mean change from Baseline in hematology parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet count, White Blood cell count
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Mean change from Baseline in hematology parameters : Hematocrit
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Mean change from Baseline in hematology parameters : Mean Corpuscle Hemoglobin
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Mean change from Baseline in hematology parameters : Hemoglobin, Mean Corpuscle Hemoglobin concentration
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Mean change from Baseline in hematology parameters : Mean Corpuscle Volume
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Mean change from Baseline in hematology parameters : Red Blood Cell count, Reticulocytes
Timeframe: Baseline (Day 1 pre-dose) and Day 28
Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration AUC(0-t) at specified time points
Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Maximum observed concentration (Cmax) at specified time points
Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Time of occurrence of Cmax (Tmax) at specified time points
Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Pre-dose (trough) concentration at the end of the dosing interval (Ct) at specified time points
Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Apparent clearance following oral dosing (CL/F) at specified time points
Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Apparent volume of distribution (V/F) at specified time points
Timeframe: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Apparent terminal elimination half-life (t1/2) at specified time points
Timeframe: The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected.
Time to first bowel movement after first dose
Timeframe: Up to Day 28
Daily bowel movement frequency
Timeframe: Up to Week 4 (Day 28)
Daily average stool consistency
Timeframe: Up to Week 4 (Day 28)
Change from Baseline in upper gastrointestinal (GI) symptoms as assessed by total Gastrointestinal Cardinal Symptom Index – Daily Diary (GCSI–DD)
Timeframe: Up to 14 days post last dose (Day 28)
Change from Baseline in Whole bowel transit time, 100 % gastric emptying time (truncated at 240 minutes), small bowel transit time, colonic transit time as determined by Wireless Motility Capsule (WMC)
Timeframe: Baseline(Screening i.e., Day -30 to -1), Day 1 and 28
Interventions:
Enrollment:
79
Primary completion date:
2013-26-02
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Gastroparesis
Product
camicinal
Collaborators
Not applicable
Study date(s)
May 2011 to February 2013
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 80 years
Accepts healthy volunteers
No
- Type I or II Diabetes Mellitus (HbA1C < 10%)
- Male or female between 18 and 80 years of age, inclusive.
- Patient has acute severe gastroenteritis
- Patient has a gastric pacemaker
Inclusion and exclusion criteria
Inclusion criteria:
- Type I or II Diabetes Mellitus (HbA1C < 10%)
- Male or female between 18 and 80 years of age, inclusive.
- Patient has gastroparesis at screening (gastric half-time of emptying > upper limit of normal as determined by 13C-oral breath test)
- Patient must have a > or = 3 month history of relevant symptoms of gastroparesis (e.g., chronic post-prandial fullness, early satiety, postprandial nausea), patients will have a mean of the daily scores over a minimum of 7 days indicating > or = mild (2) and < or = severe (4) post-prandial fullness 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 MlU/mL, or a value consistent with the local laboratory standard value, is confirmatory. OR Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 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.
- Male patients must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication through at least 5 days after the last dose of study medication.
- BMI >18 and < or = 35.0 kg/m2 (inclusive).
- Patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction or strictures 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.
- Estimated (or measured) glomerular filtration rate > or = 30 mL/min.
- QTcB or QTcF < 450 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.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- AST and ALT < 2xULN; alkaline phosphatase and bilirubin < or = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Exclusion criteria:
- Patient has acute severe gastroenteritis
- Patient has a gastric pacemaker
- Patient is on chronic parenteral feeding
- Patient has pronounced dehydration
- Recent (last 6 weeks) history of poor control of diabetes e.g. hypoglycaemia requiring medical intervention, diabetic ketoacidosis, admission for control 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 within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin), GLP-1 mimetics)
- Regular opiate use
- 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 that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical 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 time-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 females.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Trial location(s)
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02114
Status
Study Complete
Location
GSK Investigational Site
Chattanooga, Tennessee, United States, 37421
Status
Study Complete
Location
GSK Investigational Site
Chevy Chase, Maryland, United States, 20815
Status
Study Complete
Showing 1 - 6 of 22 Results
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
Study complete
Actual primary completion date
2013-26-02
Actual study completion date
2013-26-02
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
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website