FTIH to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses of GSK1322888 in Healthy Caucasian and Japanese Volunteers

NCT01294566 | Completed Phase 1

• 1 other identifier: 114422
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This study is the First Time In Human study for the motilin receptor agonist, GSK1322888. GSK1322888 is a potent and selective small molecule motilin receptor agonist, distinct from the motilide compound structures. The aims of this study are to assess the safety, tolerance, and pharmacokinetics of single oral doses of GSK1322888 and to identify a well-tolerated and safe dose that will accelerate gastric emptying of a 13C stable isotope-labeled test meal in healthy volunteers. The study will include assessment of ECGs, vital signs, safety laboratory sampling, adverse events, pharmacokinetics, and the 13C-Octanoic Acid Breath Test to measure gastric emptying.

Conditions

Gastroparesis

Keywords

safety; motilin agonist; single dose; ascending dose; GSK1322888; migrating motor complex; tolerability; FTIH; gastric emptying

Outcome Measures

Primary Outcomes (2)

• Adverse Events following single oral doses of GSK1322888

  includes abnormal clincal lab values, ECGs, vital signs

  1 week post dose

• pharmacokinetics of GSK1322888 following single, oral doses

  includes AUC, Cmax, tmax, and t1/2

  48 h post dose

Secondary Outcomes (6)

• gastric emptying of a radio-labeled test meal, as measured by the 13C-octanoic acid breath test following single oral doses of GSK1322888

  4 h

• dose/exposure response relationship for gastric emptying of a radio-labeled test meal, as measured by the 13C-octanoic acid breath test following single oral doses of GSK1322888

  48 h

• dose proportionality following single dose administration

  48 h

• steady-state PK based on single dose data

  28 h

• accumulation based on single dose data

  48 h

Study Arms (2)

Cohort 1

EXPERIMENTAL

GSK1322888 (1 mg, 2 mg, 5 mg, 10 mg; 6 subjects) and Placebo (32 subjects)

Drug: GSK1322888; Drug: Placebo

Cohort 2

EXPERIMENTAL

GSK1322888 (20 mg, 40 mg, 80 mg, and dose to be determined; 6 subjects) and Placebot (2 subjects)

Drug: GSK1322888; Drug: Placebo

Interventions

GSK1322888 DRUG

1 mg, 5 mg or 25 mg capsule

Cohort 1; Cohort 2

Placebo DRUG

matching placebo capsules

Cohort 1; Cohort 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AST, ALT, alkaline phosphatase and bilirubin \< or =1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Healthy as determined by a responsible and experienced physician
• Male or female between 18 (20 for Japanese) and 65 years of age inclusive
• Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods
• Body weight \> or = 50 kg and BMI within the range 18.5 - 29.9 kg/m2 (inclusive).
• Capable of giving written informed consent
• Average QTc, QTcB or QTcF \< 430 msec.
• For Japanese subjects Japanese ancestry defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese.

You may not qualify if:

• Hepatitis B or Hepatitis C positive
• 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 drug/alcohol screen.
• HIV positive
• History of regular alcohol consumption within 6 months of the study
• 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) prior to the first dose of study medication
• History of sensitivity to any of the study medications, or components thereof
• 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
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.
• Regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
• Subjects will be screened such that those subjects exhibiting rapid gastric emptying rates (t½b \< 75 min) will be excluded

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Links

• Results for study 114422 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Gastroparesis

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: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2011
• First Posted: February 11, 2011
• Study Start: November 29, 2010
• Primary Completion: March 23, 2011
• Study Completion: March 23, 2011
• Last Updated: June 28, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)