Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00733551
First received: August 12, 2008
Last updated: March 15, 2012
Last verified: February 2011
  Purpose

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


Condition Intervention Phase
Gastroparesis
Drug: GSK962040 oral tablets (1, 5, 10, 25 mg)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Ascending Dose Trial to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics, of Repeat Doses of Motilin Receptor Agonist GSK962040 in Male and Female Healthy Volunteers

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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)). [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effect on gastric emptying.Effect of liquid meal on PK of GSK962040. Effect on bowel movement parameters [ Designated as safety issue: No ]
  • Pharmacokinetic parameters following repeated oral doses of GSK962040 during a simulated liquid enteral feed meal: Cmax, Tmax, and AUC(0-t) [ Designated as safety issue: No ]
  • 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) [ Designated as safety issue: No ]
  • Bowel movement parameters: Time to first bowel movement after first dose, Daily bowel movement count, Daily average bowel movement Bristol Stool Form scale [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: September 2008
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1-5 Drug: GSK962040 oral tablets (1, 5, 10, 25 mg)

Active GSK962040. Planned and actual doses per cohort as follows:

Cohort 1 planned dose = 10 mg; actual dose = 10 mg Cohort 2 planned dose = 30 mg; actual dose = 20 mg Cohort 3 planned dose = 100 mg; actual dose = 50 mg Cohorts 4 and 5 planned doses to be determined.

Other Names:
  • GSK962040 oral tablets (1
  • 5
  • 10
  • 25 mg)

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Inclusion:

  • 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.
  • History of cholecystectomy or biliary tract disease.
  • History or presence of thyroid dysfunction (NOTE: subjects with abnormal TSH at screening/baseline or hypothyroidism on a stable dose of thyroid replacement therapy are not eligible).
  • A history or presence of recreational drug abuse or dependence or current abuse as evidenced by positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • History of regular alcohol consumption within 6 months of the study defined as:
  • An average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to approximately a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
  • The subject 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).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • 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 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 or pregnant females.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • For male volunteers: An unwillingness of the male subject to comply with the contraception requirements listed in the protocol, from the time of the first dose of study medication until at least 4 days following administration of the last dose of study medication.
  • History of or current lactose intolerance.
  • Subjects recruited for/participating in Cohorts 2-5 will be screened such that subjects exhibiting rapid gastric emptying rates will be excluded, as defined by the reference range of baseline gastric emptying rate (t1/2b) observed in cohort 1.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00733551

Locations
United Kingdom
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB2 2GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00733551     History of Changes
Other Study ID Numbers: MOT109681
Study First Received: August 12, 2008
Last Updated: March 15, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
oral dose
motilin
gastric emptying
GSK962040

Additional relevant MeSH terms:
Gastroparesis
Digestive System Diseases
Gastrointestinal Diseases
Neurologic Manifestations
Paralysis
Signs and Symptoms
Stomach Diseases

ClinicalTrials.gov processed this record on November 25, 2014