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
Condition: Gastroparesis
MeSH terms: Gastroparesis; Parkinson Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      Gastric emptying is the end-result of a complex and carefully regulated series of events
      which follow the ingestion of a meal, each of which is dependent on the other and subject to
      neurohormonal control. Motilin is an endogenous peptide, produced mainly in the duodenum,
      whose physiological action is mediated by motilin receptors located on enteric neurons,
      peripheral terminals of the vagus, and on the smooth muscle of the gut. Motilin and
      non-peptide agonists at motilin receptors increases the gastric emptying rate and therefore
      provide a potential approach to the treatment of a range of clinical conditions in which
      delayed gastric emptying is thought to be part of the physiopathology and may be contributory
      to symptoms. Parkinson's disease (PD) is a progressive neurodegenerative disorder
      characterized by degeneration of nigrostriatal dopaminergic neurones. It affects 1.5% of the
      global population over 65 years of age. Cardinal symptoms comprise bradykinesia, rigidity,
      resting tremors and postural instability. Gastrointestinal dysfunction, including
      gastroparesis, is a frequent feature of PD affecting approximately 90% of patients, and is
      caused by autonomic dysfunction as well as an adverse effect of antiparkinsonian drug
      therapy. The therapeutic mainstay for PD treatment is the neutral amino acid
      L-3,4-dihydroxyphenylalanine (L-DOPA), a dopamine prodrug, as it provides the most rapid and
      effective symptomatic control of motor impairment in PD. The primary determinant of L-DOPA
      bioavailability is gastric emptying (GE); delays in GE slow delivery of L-DOPA to its
      proximal small intestinal absorption sites, increasing the extent of presystemic metabolism,
      and leading to slowed and diminished absorption.
    

Detailed description: 
      MOT115816 will be conducted as a multi-center, randomized, double-blind, placebo controlled
      study to investigate the ability of the motilin receptor agonist GSK962040 to improve L-DOPA
      pharmacokinetics (PK) by enhancing gastric emptying via motilin receptor agonism. Subjects
      will be randomized to receive 50 mg GSK962040 or placebo in a 2:1 ratio administered orally
      once daily for 7-9 days. The study will consist of a screening/baseline period, a treatment
      period, and a 14-day post treatment safety follow-up visit. During this period participants
      will be asked to attend the study center for 5 visits 3 of which will last approximately 5
      hours. The duration of each patient's participation in the study from screening to follow-up
      visit will be approximately 7-8 weeks. For three of the visits, subjects will visit the
      clinical unit fasted and prior to taking their first morning L-DOPA dose. Volunteers will
      undergo a complete physical (including cardiovascular monitoring (ECG), vital signs, blood
      samples, and medical history), measurement of plasma L-DOPA levels, completion of patient
      diary to capture the amount of awake time (in hours) spent "on" without dyskinesias, "on"
      with troublesome dyskinesias, "on" with non-troublesome dyskinesias, and "off" and gastric
      symptoms, non-motor and motor symptoms assessments (MDS-UPDRS rating scale and "finger taps")
      and measurement of gastric emptying rate.
    

Intervention name(s): GSK962040 (25 mg tablet); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 25 mg tablet; matching placebo tablet
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)