Evaluation of the Safety, Tolerability and Pharmacokinetics of Repeat Oral Doses of GSK962040 Administered to Healthy Adult Subjects.

NCT00733551 | Completed Phase 1

• 1 other identifier: MOT109681
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety, tolerability and exposure of repeat escalating oral doses of GSK962040.

Conditions

Gastroparesis

Keywords

motilin; gastric emptying; GSK962040; oral dose

Outcome Measures

Primary Outcomes (1)

• Safety, tolerability, and PK of GSK962040 from all adverse event reporting, 12-lead ECGs, vital signs, observation, safety laboratory tests and GI symptom diary; (AUC, Cmax, Tmax, accumulation ratio (Ro), half life and time invariance ratio (Rs)).

Secondary Outcomes (5)

• Effect on gastric emptying.Effect of liquid meal on PK of GSK962040. Effect on bowel movement parameters

• Pharmacokinetic parameters following repeated oral doses of GSK962040 during a simulated liquid enteral feed meal: Cmax, Tmax, and AUC(0-t)

• Gastric emptying, as measured by the 13C octanoic acid breath test:Gastric half emptying time (t1/2b), Duration of the lag time (tlag), Gastric evacuation coefficient (GEC)

• Bowel movement parameters: Time to first bowel movement after first dose, Daily bowel movement count, Daily average bowel movement Bristol Stool Form scale

• Pharmacokinetic parameters following repeated every other day (QOD) oral doses of GSK962040: Cmax, Tmax, AUC(0-t), accumulation ratio (Ro), and, if possible, half-life, and time invariance ratio (Rs), as needed.

Study Arms (4)

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.

Drug: GSK962040; Drug: Placebo

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.

Drug: GSK962040; Drug: Placebo

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.

Drug: GSK962040; Drug: Placebo

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.

Drug: GSK962040; Drug: Placebo

Interventions

GSK962040 DRUG

GSK962040 tablets will be available in dosing strengths of 1 milligram, 5 milligrams, 25 milligrams given orally, once daily, in the morning, in a fasted state.

Subjects receiving GSK962040 in cohort 1; Subjects receiving GSK962040 in cohort 2; Subjects receiving GSK962040 in cohort 3; Subjects receiving placebo in cohort 1, 2 and 3

Placebo DRUG

Placebo tablets will be given orally, once daily, in the morning, in a fasted state.

Subjects receiving GSK962040 in cohort 1; Subjects receiving GSK962040 in cohort 2; Subjects receiving GSK962040 in cohort 3; Subjects receiving placebo in cohort 1, 2 and 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as determined by a physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. In any case, liver function tests must be strictly within the normal range at screening.
• Male or female between 18 and 55 years of age, inclusive.
• Non-smoker for at least 6 months based on smoking history.
• A female subject 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 is confirmatory.
• Child-bearing potential and agrees to use one of the contraception methods listed in the protocol 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 subjects must agree to use contraception for at least 4 days following the last dose of study medication.
• Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication through at least 4 days after the last dose of study medication.
• Body weight \> 50 kg and BMI within the range 18.5 - 29.9 kg/m2 (inclusive).
• QTcB or QTcF \< 450 msec or QTc\<480msec in subjects with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period.
• Normal physical examination (physical exam demonstrates no evidence of clinically active disease or physical or mental impairment). A subject with a clinical abnormality may be included only if the Principal Investigator or physician designee considers that the abnormality will not introduce additional risk factors and will not interfere with the study procedures. Consultation with the GSK medical monitor is required before such subjects may be included.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Subjects will have negative Helicobacter pylori status or have received eradication within the last calendar year.
• History or presence of any clinically significant metabolic condition, gastrointestinal (including passing of \> 3 stools/ day or \<3 stools/week) condition or endocrinological condition.
• 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.
• History of major gastrointestinal surgical procedure within the last 10 years.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, Cambridgeshire, CB2 2GG, United Kingdom

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study MOT109681 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Gastroparesis

Interventions

N-(3-fluorophenyl)-1-((4-(((3S)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine

Condition Hierarchy (Ancestors)

Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2008
• First Posted: August 13, 2008
• Study Start: September 23, 2008
• Primary Completion: July 20, 2009
• Study Completion: July 20, 2009
• Last Updated: July 18, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)