GastroparesisPhase 2NCT01262898
Dose Response of 28 Days of Dosing of GSK962040 in Type I and II Diabetic Male and Female Subjects With Gastroparesis
A Phase 2 study testing GSK962040 (5 mg tablet), GSK962040 (25 mg tablet) and GSK962040 (125 mg tablet) in people with Gastroparesis, run by GlaxoSmithKline at 22 sites in 6 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Gastroparesis
- What is being tested?
- GSK962040 (5 mg tablet), GSK962040 (25 mg tablet) and GSK962040 (125 mg tablet)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 22 sitesin 6 countries
- Study dates
- 3 May 2011to 26 Feb 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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%).
Who cannot join
- 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)
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- 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 locations and contacts
22 sites in 6 countries.
22 sites in 6 countries
United States9 sites
GSK Investigational Site
Boston, Massachusetts, 02114
GSK Investigational Site
Chattanooga, Tennessee, 37421
GSK Investigational Site
Chevy Chase, Maryland, 20815
GSK Investigational Site
Concord, California, 94520
GSK Investigational Site
Great Neck, New York, 11023
GSK Investigational Site
Indianapolis, Indiana, 46202
GSK Investigational Site
Milwaukee, Wisconsin, 53215
GSK Investigational Site
Richmond, Virginia, 23294
GSK Investigational Site
San Antonio, Texas, 78258
United Kingdom5 sites
GSK Investigational Site
Cambridge, CB2 2GG
GSK Investigational Site
Dundee, DD1 9SY
GSK Investigational Site
London, W12 0HS
GSK Investigational Site
London, W1G 6AD
GSK Investigational Site
Salford, M6 8HD
Canada4 sites
GSK Investigational Site
Calgary, Alberta, T2N 4N1
GSK Investigational Site
Edmonton, Alberta, T6G 2E1
GSK Investigational Site
Thornhill, Ontario, L4J 8L7
GSK Investigational Site
Toronto, Ontario, M4G 3E8
Belgium2 sites
GSK Investigational Site
Brussels, 1090
GSK Investigational Site
Leuven, 3000
About this study
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
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.
- Conditions
- Gastroparesis
- Being tested
- GSK962040 (5 mg tablet), GSK962040 (25 mg tablet), GSK962040 (125 mg tablet), Placebo
- Keywords
- tolerability, pharmacokinetics, 13 C oral breath test, Type I and II Diabetes mellitus, gastroparesis, gut motility, phase II, pharmacodynamics, repeat dose, gastric emptying, symptoms, GSK962040
- Medical subject headings
- Gastroparesis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK962040 (5 mg tablet)Drug
5 mg tablet
GSK962040 (25 mg tablet)Drug
25 mg tablet
GSK962040 (125 mg tablet)Drug
125 mg tablet
PlaceboDrug
matching placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| GSK962040 (10 mg) | Experimental | GSK962040 10 mg Receives: Drug: GSK962040 (5 mg tablet) |
| GSK962040 (50 mg) | Experimental | GSK962040 50 mg Receives: Drug: GSK962040 (25 mg tablet) |
| GSK962040 (125 mg) | Experimental | GSK962040 125 mg Receives: Drug: GSK962040 (125 mg tablet) |
| Placebo | Experimental | Placebo Receives: Drug: GSK962040 (5 mg tablet); Drug: GSK962040 (25 mg tablet); Drug: GSK962040 (125 mg tablet); Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gastric Half Emptying Time (GEt1/2)
Gastric half emptying time is the time taken for half the contents of the stomach to empty. Gastric emptying was measured using the 13C-oral breath test, which is a tracer method that utilizes 13C, a non-radioactive isotope. Basal breath samples were obtained after an overnight fast or otherwise after 4 hours of fasting following a light meal. On Day 1 and Day 28, participants were then dosed with GSK962040 and additional breath test samples were taken prior to administration of a 13C-labelled test meal. The test meal was consumed approximately 80 minutes(min) later. After consumption of the test meal, breath samples were collected at pre-specified time points over an approximately 4 hour period following the test meal. For the duration of the breath test, no food or drink were allowed. The 13C breath content was determined by isotope ratio mass spectrometry. GE t1/2 was determined by using the cumulative percentage of the administered dose of 13C excreted in breath over 4 hours.
Measured: Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28
Secondary outcomes (29)
Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs)
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Data for on-treatment adverse events is reported.
Measured: 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
Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline, Day 1, and Day 8
Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position
Heart rate measurements were taken at pre-dose and 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values . Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline, Day 1, and Day 8
Change From Baseline in Electrocardiography Parameters (12-lead ECG)
ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The Baseline value was the Day 1 pre-dose value. ECG parameters included PR interval, QRS duration, QT interval, QTcB, QTcF and RR interval.
Measured: Baseline, Day 1 and Day 28
Number of Participants Outside the Normal Range for SBP and DBP
Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The clinical concern range (CCR) for SBP was greater than (<) 85 and less than (>) 160 and for DBP the range was <45 and >100. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values.
Measured: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Number of Participants Outside the Normal Range for Heart Rate
Heart rate measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The CCR for heart rate was Increase or decrease by less than or equal to (>=) 15 and >= 30. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values.
Measured: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Number of Participants Outside the Normal Range for 12-lead ECG
ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The CCR for ECG parameters were: PR interval (<110 and >220), QRS interval (<75 and >110), Absolute QTc interval (>450 to =< 480) respectively. Baseline was the pre-dose reading for Day 1. Data for abnormal- clinically significant (ACS) and abnormal- not clinically significant (ANCS) has been presented.
Measured: 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
Alkaline phosphatase, alanine amino transferase, aspartate amino transferase, gamma glutamyl transferase, creatine kinase, lactate dehydrogenase measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: 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
Direct Bilirubin, Total Bilirubin, Creatinine, Uric acid measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein
Albumin, Total Protein measurements were taken at Baseline (Day 1 pre-dose), and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: 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
Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon dioxide content/Bicarbonate measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: 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
Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet count, White Blood cell count measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Hematocrit
Hematocrit measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin
Mean Corpuscle Hemoglobin measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration
Hemoglobin, Mean Corpuscle Hemoglobin concentration measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume
Mean Corpuscle Volume measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes
Red Blood Cell count, Reticulocytes measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: 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
AUC(0-t) was derived from GSK962040 plasma concentration-time data. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.Only participants who received GSK962040 drug were analyzed.
Measured: 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
Cmax is defined as the maximum observed drug concentration after administration. Cmax was determined directly from the raw concentration-time data. Samples were collected at the following times: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose.
Measured: 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
Tmax is defined as the time to reach the observed maximum concentration. Samples were collected at the following times: Tmax was determined directly from the raw concentration-time data. Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose.
Measured: 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
Analysis of pre-dose (trough) concentration at the end of the dosing interval (Ct) was planned to be performed from the 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.
Measured: 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
CL/F was calculated as dose/AUC. The parameter was planned to be analyzed from 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.
Measured: 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
The apparent volume of distribution V/F = CL/F × MRT, where MRT is the mean residence time. 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.
Measured: 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
This outcome measure was not analyzed in results.
Measured: 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
The time to first bowel movement was calculated as the time of the first bowel movement after the first dose in hours (floored) for each participant. If a participant had fewer than 5 days worth of data then the daily mean for that week was set to missing for the following two parameters: Bowel Movement Count and Stool Consistency. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics of time to first bowel movement.
Measured: Up to Day 28
Daily Bowel Movement Frequency
Daily bowel movement frequency analyzed number of times passed stools in 24 hours of duration. Following dosing with study medication, stool monitoring was performed up to Day 28. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics.
Measured: Up to Week 4 (Day 28)
Daily Average Stool Consistency
Stool consistency was determined on a scale of 1 to 5 (1 = Very hard, 2 = Hard, 3 = Formed, 4 = Loose, 5 = Watery). Following dosing with study medication, stool monitoring was performed up to Day 28. Participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics.
Measured: 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)
GCSI-DD was measured on a 6-point scale. The Total GCSI-DD score was the mean of the following three subscales: Nausea/Vomiting Subscale = mean (nausea, retching, vomiting), Fullness/Early Satiety Subscale = mean (feeling excessively full after meals, not able to finish a normal-sized meal, stomach fullness, loss of appetite), Bloating Subscale = mean (bloating, stomach or belly visibly larger). Each subscale was scored on a severity scale of 0 (none) to 5 (very severe), with lower scores representing less symptom severity. The change from Baseline to each study week in average score was derived and if it improved by 1 point or more, that participant was defined as "responder" for that symptom and on that particular week. Baseline was Screening2/Baseline values (Day -30 to -1). Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: 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)
WMC is an ingestible telemetric capsule which measures pH, pressure and temperature to assess total gastric emptying time, small and large bowel transit time, colonic transit time, and whole gut transit time. The WMC was ingested immediately following the standard test meal for the oral breath test. Data was collected on a data logger, which was worn on a belt clip. The WMC passed naturally in the participant's stools between 2 and 5 days after ingestion. The parameters Whole bowel transit time, 100 % gastric emptying time (truncated at 240 minutes), small bowel transit time, colonic transit time were analyzed. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Measured: Baseline(Screening i.e., Day -30 to -1), Day 1 and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2010 (estimated)
- Study start3 May 2011
- Primary completion26 Feb 2013
- Study completion26 Feb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GastroparesisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01262898
- Sponsor's protocol ID
- 114479
- Other IDs
- 2010-023186-21
- Status last verified
- Jul 2021
- First submitted
- 16 Dec 2010
- Last updated
- 15 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD for this study is available via the Clinical Study Data Request site
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01262898
- Acronym / sponsor ID
- 114479
- Conditions
- Gastroparesis
- Keywords
- tolerability, pharmacokinetics, 13 C oral breath test, Type I and II Diabetes mellitus, gastroparesis, gut motility, phase II, pharmacodynamics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 3 May 2011 (actual)
- Primary completion
- 26 Feb 2013 (actual)
- Study completion
- 26 Feb 2013 (actual)
- First posted
- 17 Dec 2010 (estimated)
- Results
- Posted 13 Oct 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GSK962040 (10 mg) | Experimental | Drug: GSK962040 (5 mg tablet)GSK962040 10 mg |
| GSK962040 (50 mg) | Experimental | Drug: GSK962040 (25 mg tablet)GSK962040 50 mg |
| GSK962040 (125 mg) | Experimental | Drug: GSK962040 (125 mg tablet)GSK962040 125 mg |
| Placebo | Experimental | Drug: GSK962040 (5 mg tablet), Drug: GSK962040 (25 mg tablet), Drug: GSK962040 (125 mg tablet), Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK962040 (5 mg tablet)5 mg tablet | Drug | GSK962040 (10 mg), Placebo |
| GSK962040 (25 mg tablet)25 mg tablet | Drug | GSK962040 (50 mg), Placebo |
| GSK962040 (125 mg tablet)125 mg tablet | Drug | GSK962040 (125 mg), Placebo |
| Placebomatching placebo tablet | Drug | Placebo |
Primary outcome
Gastric Half Emptying Time (GEt1/2)
Time frame: Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28
Gastric half emptying time is the time taken for half the contents of the stomach to empty. Gastric emptying was measured using the 13C-oral breath test, which is a tracer method that utilizes 13C, a non-radioactive isotope. Basal breath samples were obtained after an overnight fast or otherwise after 4 hours of fasting following a light meal. On Day 1 and Day 28, participants were then dosed with GSK962040 and additional breath test samples were taken prior to administration of a 13C-labelled test meal. The test meal was consumed approximately 80 minutes(min) later. After consumption of the test meal, breath samples were collected at pre-specified time points over an approximately 4 hour period following the test meal. For the duration of the breath test, no food or drink were allowed. The 13C breath content was determined by isotope ratio mass spectrometry. GE t1/2 was determined by using the cumulative percentage of the administered dose of 13C excreted in breath over 4 hours.
29 secondary outcomes
Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs)
Time frame: 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
Time frame: Baseline, Day 1, and Day 8
Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position
Time frame: Baseline, Day 1, and Day 8
Change From Baseline in Electrocardiography Parameters (12-lead ECG)
Time frame: Baseline, Day 1 and Day 28
Number of Participants Outside the Normal Range for SBP and DBP
Time frame: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Number of Participants Outside the Normal Range for Heart Rate
Time frame: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Number of Participants Outside the Normal Range for 12-lead ECG
Time frame: 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
Time frame: 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
Time frame: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein
Time frame: 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
Time frame: 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
Time frame: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Hematocrit
Time frame: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin
Time frame: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration
Time frame: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume
Time frame: Baseline (Day 1 pre-dose) and Day 28
Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Up to Day 28
Daily Bowel Movement Frequency
Time frame: Up to Week 4 (Day 28)
Daily Average Stool Consistency
Time frame: 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)
Time frame: 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)
Time frame: Baseline(Screening i.e., Day -30 to -1), Day 1 and 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
22 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK962040 (5 mg tablet), GSK962040 (25 mg tablet) and GSK962040 (125 mg tablet) in people with Gastroparesis, run by GlaxoSmithKline at 22 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, United Kingdom, Canada, Belgium, Australia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gastric Half Emptying Time (GEt1/2) (time frame: Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.