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

NCT01607385 | Completed Phase 1

• 1 other identifier: 116511
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Keywords

pharmacokinetic; intestinal bile acid transporter inhibitor; GSK2330672; pharmacodynamic; GSK1614235; dose escalation

Outcome Measures

Primary Outcomes (4)

• Adverse events

  3 weeks

• Clinical laboratory tests for safety.

  Regular clinical chemistry and hematology panels.

  7 weeks

• Bristol Stool Form Scale

  Frequency of bowel movements and quality of stool samples.

  2 weeks

• Gastrointestinal Symptom Rating Scale

  Tolerability of possible gastic side effets.

  2 weeks

Secondary Outcomes (2)

• Pharmacokinetic measures of GSK2330672.

  Change from baseline at 2 weeks.

• Pharmcokinetic measures of GSK2330672, GSK1614235, GSK2313533, and GSK2313537.

  Full profiles on Day 13.

Study Arms (2)

GSK2330672

ACTIVE COMPARATOR

Drug: GSK2330672; Drug: GSK1614235

Placebo

PLACEBO COMPARATOR

Drug: Placebo; Drug: GSK1614235

Interventions

GSK2330672 DRUG

BID, repeat doses

GSK2330672

Placebo DRUG

BID, repeat doses

Placebo

GSK1614235 DRUG

BID, co-dosed BID with last dosing day of active/placebo repeat doses

GSK2330672; Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

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 116511 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

3-((((3R,5R)-3-butyl-3-ethyl-7-(methyloxy)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl)methyl)amino)pentanedioic acid

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 17, 2012
• First Posted: May 30, 2012
• Study Start: May 18, 2012
• Primary Completion: December 3, 2012
• Study Completion: December 3, 2012
• Last Updated: July 26, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)