A Study to Evaluate the Safety, Tolerability, Pharmacokinetic a Single Day of Dosing With GSK1614235.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01607385
First received: May 17, 2012
Last updated: March 7, 2013
Last verified: February 2013
  Purpose

A single blind, randomized, placebo-controlled, dose escalating study to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic parameters of repeat doses of GSK2330672 in healthy volunteers, given alone and with a single day of dosing with GSK1614235


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: GSK2330672
Drug: Placebo
Drug: GSK1614235
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Single Blind, Randomized, Placebo-controlled, Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Parameters of Repeat Doses of GSK2330672 in Healthy Volunteers, Given Alone and With a Single Day of Dosing With GSK1614235

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Adverse events [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
  • Clinical laboratory tests for safety. [ Time Frame: 7 weeks ] [ Designated as safety issue: Yes ]
    Regular clinical chemistry and hematology panels.

  • Bristol Stool Form Scale [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    Frequency of bowel movements and quality of stool samples.

  • Gastrointestinal Symptom Rating Scale [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
    Tolerability of possible gastic side effets.


Secondary Outcome Measures:
  • Pharmacokinetic measures of GSK2330672. [ Time Frame: Change from baseline at 2 weeks. ] [ Designated as safety issue: No ]
    AUC, Cmax, tmax, t1/2

  • Pharmcokinetic measures of GSK2330672, GSK1614235, GSK2313533, and GSK2313537. [ Time Frame: Full profiles on Day 13. ] [ Designated as safety issue: No ]
    AUC, Cmax, tmax and t1/2


Enrollment: 56
Study Start Date: May 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: GSK2330672
NA
Drug: GSK2330672
BID, repeat doses
Drug: GSK1614235
BID, co-dosed BID with last dosing day of active/placebo repeat doses
Placebo Comparator: Placebo
NA
Drug: Placebo
BID, repeat doses
Drug: GSK1614235
BID, co-dosed BID with last dosing day of active/placebo repeat doses

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible and experienced 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. Laboratory assessments may be repeated if outside of normal ranges. The Investigator may interpret screening vital sign data based on the subject's age, physical state and level of fitness. Subjects with vital sign readings marginally outside the normal ranges below may be included in the study if in the Investigator's opinion these values are not clinically significant and will not present a safety risk or affect study assessments.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Subjects must understand the aims, investigational procedures and possible consequences of the study and must be able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
  • Male or female between 18 and 60 years of age inclusive, at the time of signing the informed consent.
  • 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 greater than 40 MlU/ml and estradiol less than 40 pg/ml (less than 140 pmol/L) is confirmatory in the absence of a clear postmenopausal history; Females on hormone replacement therapy must discontinue hormone replacement therapy to allow confirmation of post-menopausal status prior to study enrollment. For most forms of hormone replacement therapy, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of hormone replacement therapy. Following confirmation of their post-menopausal status, they can resume use of hormone replacement therapy during the study.
  • Body mass index within the range 19 - 32kg/m2 (inclusive).

Exclusion Criteria:

  • ALT, alkaline phosphatase and bilirubin greater than 1.5xULN (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%.
  • Current or chronic history of inflammatory bowel disease, chronic diarrhea, Crohn's disease or malabsorption syndromes.
  • Current or chronic history of cholelithiasis, inflammatory gall bladder disease, cholestatic liver injury, and cholecystectomy.
  • Current or chronic history of liver disease, or known hepatic abnormalities (with the exception of Gilbert's syndrome).
  • Fecal occult blood positive test at screening.
  • Triglycerides greater than 250mg/dL.
  • History of chronic or acute pancreatitis.
  • Mean QTc greater than and equal to 450msec on three tracings obtained at least 5 minutes apart.
  • 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.
  • A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 14 drinks for males or greater than 7 drinks for females. One drink is equivalent to 12g of alcohol: 12 ounces (360mL) of beer, 5 ounces (150mL) of wine or 1.5 ounces (45mL) of 80 proof distilled spirits.
  • 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 or 5 half-lives of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Unable to refrain from the 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 500mL within a 56-day period.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01607385

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01607385     History of Changes
Other Study ID Numbers: 116511
Study First Received: May 17, 2012
Last Updated: March 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
pharmacokinetic
intestinal bile acid transporter inhibitor
GSK2330672
pharmacodynamic
GSK1614235
dose escalation

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on April 16, 2014