Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01602549 | A Study to Assess the Effect of Repeat Doses of GSK962040 on the Pharmacokinetics of L-DOPA in Subjects With Parkinson's Disease Exhibiting Delayed Gastric Emptying | PHASE2 | COMPLETED | 58 | — | — | Jul 1, 2012 | May 1, 2014 | Feb 6, 2017 | 11 | Australia, Germany +2 |
| NCT01262898 | Dose Response of 28 Days of Dosing of GSK962040 in Type I and II Diabetic Male and Female Subjects With Gastroparesis | PHASE2 | COMPLETED | 79 | — | — | May 3, 2011 | Feb 26, 2013 | Jul 15, 2021 | 22 | United States, Australia +4 |
| NCT01039805 | Evaluation of Single Doses of GSK962040 in Critically Ill Patients With Enteral Feed Intolerance | PHASE2 | COMPLETED | 34 | — | — | Dec 1, 2009 | Jul 1, 2011 | Jan 30, 2017 | 1 | Australia |
| NCT00861809 | The Effect of Single Doses of the Motilin Receptor Agonist GSK962040 in Type I Diabetic Patients With Gastroparesis | PHASE2 | COMPLETED | 11 | — | — | Jun 1, 2009 | Nov 1, 2010 | Jan 30, 2017 | 2 | Belgium, Sweden |
| NCT01039974 | GSK962040 Drug-drug Interaction Study With Ketoconazole | PHASE1 | COMPLETED | 6 | — | — | Sep 18, 2009 | Nov 30, 2009 | Jun 20, 2017 | 1 | United States |
| NCT00733551 | Evaluation of the Safety, Tolerability and Pharmacokinetics of Repeat Oral Doses of GSK962040 Administered to Healthy Adult Subjects. | PHASE1 | COMPLETED | 31 | — | — | Sep 23, 2008 | Jul 20, 2009 | Jul 18, 2017 | 1 | United Kingdom |
| NCT00562848 | A Study to Evaluate Safety, Side Effects, Muscle Activity and Speed of Gastric Emptying of GSK962040 | PHASE1 | COMPLETED | 48 | — | — | Sep 10, 2007 | Jun 27, 2008 | Aug 8, 2017 | 1 | Belgium |
Dose-normalized L-DOPA AUC(0-4) was derived from L-DOPA plasma concentration-time data. AUC is a measure of levodopa exposure.
Dose-normalized L-DOPA AUC(0-4) was derived from L-DOPA plasma concentration-time data. The adjusted means and ratios (GSK962040 50 mg: Placebo) were estimated using a mixed model fitting treatment, visit, treatment\*visit, Baseline L-dopa pharmacokinetic (PK) parameter, and Baseline gastric emptying half-time as fixed effects, and participant as a random effect. AUC is a measure of levodopa exposure
Dose-normalized L-DOPA Cmax was derived from L-DOPA plasma concentration-time data.
Dose-normalized L-DOPA Cmax was derived from L-DOPA plasma concentration-time data. The adjusted means and ratios were estimated using a mixed model fitting treatment, visit, treatment\*visit, Baseline L-dopa PK parameter, and Baseline gastric emptying half-time as fixed effects, and participant as a random effect.
L-DOPA Tmax was derived from L-DOPA plasma concentration-time data.
L-DOPA t1/2 was derived from L-DOPA plasma concentration-time data. This endpoint was not assessed because there were insufficient L-DOPA data/profiles to calculate this parameter.
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.
| Arm | Type | Description |
|---|---|---|
| Cohort | EXPERIMENTAL | 1:2 ratio, placebo, 50 mg administered orally once daily for 7-9 days |
| GSK962040 (10 mg) | EXPERIMENTAL | GSK962040 10 mg |
| GSK962040 (50 mg) | EXPERIMENTAL | GSK962040 50 mg |
| GSK962040 (125 mg) | EXPERIMENTAL | GSK962040 125 mg |
| Placebo | EXPERIMENTAL | Placebo |
| Cohort 1 | EXPERIMENTAL | Subjects randomized to either GSK962040 (50 mg) or placebo |
| Cohort 2 | EXPERIMENTAL | Subjects randomized to either GSK962040 (75 mg) or placebo |
| Cohort 1 Period 1 | EXPERIMENTAL | All patients will receive placebo and 2 of the 3 possible doses of GSK962040 in a randomized, double blind, placebo controlled, incomplete block, three period crossover design. |
| Cohort 1 Period 2 | EXPERIMENTAL | All patients will receive placebo and 2 of the 3 possible doses of GSK962040 in a randomized, double blind, placebo controlled, incomplete block, three period crossover design. |
| Cohort 1 Period 3 | EXPERIMENTAL | All patients will receive placebo and 2 of the 3 possible doses of GSK962040 in a randomized, double blind, placebo controlled, incomplete block, three period crossover design. |
| Cohorts 1-2 | EXPERIMENTAL | Cohorts 1 and 2 will complete both periods Period 1 GSK962040 single dose Period 2 Ketoconazole repeat dose (10 days), GSK962040 single dose |
| Subjects receiving GSK962040 in cohort 1 | EXPERIMENTAL | Eligible subjects will receive repeat oral doses of GSK962040 given as 10 milligrams once daily tablet for 14 days. |
| Subjects receiving GSK962040 in cohort 2 | EXPERIMENTAL | Eligible subjects will receive repeat oral doses of GSK962040 given as 30 milligrams once daily tablet for 14 days. |
| Subjects receiving GSK962040 in cohort 3 | EXPERIMENTAL | Eligible subjects will receive repeat oral doses of GSK962040 given as 100 milligrams once daily tablet for 14 days. |
| Subjects receiving placebo in cohort 1, 2 and 3 | PLACEBO_COMPARATOR | Eligible subjects will receive repeat oral doses of placebo tablets given once daily for 14 days in cohort 1, 2 and 3. |
| Subjects enrolled in single dose escalation cohort | EXPERIMENTAL | Subjects will receive escalated doses of GSK962040 with a starting dose of 1 milligrams along with placebo in fasted state. |
| Subjects enrolled in gastric emptying cohort | EXPERIMENTAL | Subjects will receive escalated doses of GSK962040 with a starting dose of 1 milligrams along with placebo in fasted state. |
| Subjects enrolled in gastro-enteral contractility cohort | EXPERIMENTAL | Eligible subjects will receive GSK962040 and placebo in the fasted state in crossover manner. |
| Name | Type | Description |
|---|---|---|
| GSK962040 (25 mg tablet) | DRUG | 25 mg tablet |
| Placebo | DRUG | matching placebo tablet |
| GSK962040 (5 mg tablet) | DRUG | 5 mg tablet |
| GSK962040 (125 mg tablet) | DRUG | 125 mg tablet |
| GSK962040 (50 mg) | DRUG | Cohort 1 = 50 mg |
| GSK962040 (75 mg) | DRUG | Cohort 2 = 75 mg |
| GSK962040 25 mg | DRUG | 25 mg |
| GSK962040 50 mg | DRUG | 50 mg |
| GSK962040 1250 mg | DRUG | 125 mg |
| GSK962040 | DRUG | GSK962040. Planned doses per cohort as follows: Cohort 1 planned dose = 10 mg; Cohort 2 to be determined based on data from Cohort 1 |
| Ketoconazole | DRUG | 400 mg |
Inclusion Criteria: * Diagnosis of idiopathic Parkinson's Disease (according to modified Hoehn \& Yahr criteria Stages II-IV) and with suboptimal motor control on L-DOPA or L-DOPA combination therapy (i.e. wearing off, peak dose dyskinesias, delayed on or no-on effects) * Subjects receiving a stabl...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Vanda Pharmaceuticals Inc. | VNDA | 1 | PHASE4 | Tradipitant |
| United Therapeutics Corporation | UTHR | 1 | PHASE4 | Undisclosed |