A Study in Healthy Volunteers of Single Doses of Orally Administered Investigational Product to Investigate Safety, Tolerability, and Pharmacokinecs.

A Study in Healthy Volunteers of Single Doses of Orally Administered GSK1292263 to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Compound Alone and When Co-administered With Sitagliptin

This study is the first study in humans to assess the safety and tolerability of various doses of GSK1292263 alone, and taken with sitigliptan.

Study Overview

• Status: Completed
• Conditions: Dyslipidaemias
• Intervention / Treatment: Drug: an undetermined dose of GSK1292263; Drug: ascending dose of GSK1292263; Drug: ascending dose of GSK1292263; Drug: ascending dose of GSK1292263

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Male or female between 18 and 55 years of age
• A female subject is eligible to participate if she is of non-childbearing potential
• Male subjects must agree to use one of the contraception methods listed in the protocol
• BMI within the range 20 - 29.9 kg/m2
• Capable of giving written informed consent, which includes compliance with protocol
• QTcB or QTcF < 450msec.

Exclusion Criteria:

• The subject has a positive pre-study drug/alcohol screen
• Positive urinary cotinine levels or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• History of regular alcohol consumption within 6 months of the study
• History of sensitivity to heparin or heparin-induced thrombocytopenia
• Unable or unwilling to abstain from caffeine-or xanthine-containing products for 24 hours prior to dosing until the final post-dose assessment at each treatment level.
• Use of illicit drugs.
• Use of alcohol for 24 hours prior to dosing until final post-dose assessment at each treatment level.
• Consumption of red wine, oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until collection of the final pharmacokinetic and pharmacodynamic blood samples
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
• A positive test for HIV antibody
• Pregnant females as determined by positive urine hCG test at screening or prior to dosing
• Lactating females
• Has a fasting triglyceride level >400mg/dL (4.45mmol/L)
• Has anemia defined by hemoglobin concentration <11.0g/dL for males or <10.0g/dL for females.
• CPK values higher than 2.5 times the upper limit of normal at screening.
• Significant ECG abnormalities
• abnormal vital signs as defined in the
• History of any gastrointestinal or hepatic conditions that could impact absorption of the investigational compound.
• Family history (first or second degree relatives) with a history of hypertrophic cardiomyopathy.
• Family history of torsade de pointes or other ventricular arrhythmias.
• Family history of unexplained sudden death.
• Evidence of early depolarization (e.g., Wolf-Parkinson-White syndrome).
• Has clinically significant rhythm abnormalities identified during 24-hour Screening Holter assessment.
• Subjects who have asthma or a history of asthma
• The subject has participated in a clinical trial and has received an investigational product within a protocol defined period
• 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 within 7 days or 14 days if the drug is a potential enzyme inducer or 5 half-lives 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
• Subjects who are taking low-dose aspirin for cardiovascular prophylaxis (81mg or less) are eligible to participate in the study, but the aspirin must be discontinued from Screening to the Follow-up visit
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
• Unwillingness or inability to follow the procedures outlined in the protocol.
• As a result of the medical interview, physical examination, or screening investigations, the investigator considers the subject unfit for the study.
• Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 6 active 2 placebo	Drug: an undetermined dose of GSK1292263; GSK investigational product or placebo
Experimental: Cohort 2; 9 active 3 placebo	Drug: ascending dose of GSK1292263; Ascending dose based on target exposures or placebo; Drug: ascending dose of GSK1292263; An ascending dose based on target exposure; Drug: ascending dose of GSK1292263; An ascending dose based on target exposures.
Experimental: Cohort 3; Optional cohort	Drug: ascending dose of GSK1292263; Ascending dose based on target exposures or placebo; Drug: ascending dose of GSK1292263; An ascending dose based on target exposure; Drug: ascending dose of GSK1292263; An ascending dose based on target exposures.
Experimental: Cohort 4; 12 active	Drug: ascending dose of GSK1292263; Ascending dose based on target exposures or placebo; Drug: ascending dose of GSK1292263; An ascending dose based on target exposure; Drug: ascending dose of GSK1292263; An ascending dose based on target exposures.
Experimental: Cohort 5; 12 active	Drug: ascending dose of GSK1292263; Ascending dose based on target exposures or placebo; Drug: ascending dose of GSK1292263; An ascending dose based on target exposure; Drug: ascending dose of GSK1292263; An ascending dose based on target exposures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability parameters including adverse events, clinical laboratory, electrocardiogram, and vital signs assessments.	Up to 4 days
Pharmacokinetic parameters, maximum observed plasma drug concentration, time to maximum observe.	Up to 4 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamic endpoints	Up to four days.
• Pharmacokinetic parameters following a dose, with and without food, and bioavailability	Up to four days.
Relationships betwen drug exposures and pharmacodynamic parameters, safety, and tolerability, as appropriate.	Up to four days.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2008
• Primary Completion (Actual): March 31, 2009
• Study Completion (Actual): March 31, 2009

Study Registration Dates

• First Submitted: October 27, 2008
• First Submitted That Met QC Criteria: October 30, 2008
• First Posted (Estimate): October 31, 2008

Study Record Updates

• Last Update Posted (Actual): July 7, 2017
• Last Update Submitted That Met QC Criteria: July 5, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; pharmacodynamics
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias
• Other Study ID Numbers: 111596

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 111596
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 111596
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 111596
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: 111596
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 111596
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 111596
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 111596
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register