To Investigate the Safety, Tolerability and Pharmacodynamics of GSK2890457 in Healthy Volunteers and Subjects With Type 2 Diabetes

NCT ID: NCT01725126

Last Updated: 2017-12-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-10
• Study Completion Date: 2013-09-12

Brief Summary

This study is the first administration of GSK2890457 in humans. The study will be conducted in 3 parts: - Part A (conducted at a single investigative site) will determine the safety and tolerability of GSK2890457 alone in healthy subjects during six weeks of dosing, as well as evaluating the potential for a pharmacokinetic interaction with metformin. Part A consists of Screening, Treatment (6 weeks) and Follow-up periods. - Part B (conducted at multiple sites) will determine safety, tolerability, and pharmacodynamics (PD) in subjects with Type 2 diabetes (T2D) when co-dosed for six weeks with liraglutide (Victoza). Part B consists of Screening, Run-in (1 week), Stabilization (12 weeks), Treatment (6 weeks) and Follow-up periods. - Part C (conducted at multiple sites) will determine safety, tolerability, and PD in subjects with T2D when co-dosed for 6 weeks with metformin. Part C consists of Screening, Run-in (1 week), Stabilization (12 weeks), Treatment (6 weeks) and Follow-up periods.

Conditions

Obesity

Keywords

metformin; diabetes; obesity; liraglutide

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part A - GSK2890457

Subjects will titrate up from a maximially tolerated dose over a 7-day period. Treatment Period is 6 weeks

Group Type: EXPERIMENTAL

GSK2890457

Intervention Type: DRUG

Provided as powder and capsule.

Metformin

Intervention Type: DRUG

Tablet

Part A: Single doses on Day 1 and Day 42 orally

Part B: Subject continues usual metformin dose through Run-in, and resumes after Treatment Period completed

Part C: Subject continues usual metformin dose throughout study

Part B - GSK2890457 + Liraglutide

Subjects will titrate up from a maximially tolerated dose over a 7-day period. Treatment Period is 6 weeks

Group Type: EXPERIMENTAL

GSK2890457

Intervention Type: DRUG

Provided as powder and capsule.

Liraglutide

Intervention Type: DRUG

Provided as Injection. 6mg/mL, 3mL injector pen that permits doses of 0.6mg, 1.2mg, and 1.8mg

Subcutaneous injection 18 weeks dosing (Stabilization and Treatment Periods, Part B only

Part C - GSK2890457 + Metformin

Subjects will titrate up from a maximially tolerated dose over a 7-day period. Treatment Period is 6 weeks

Group Type: EXPERIMENTAL

GSK2890457

Intervention Type: DRUG

Provided as powder and capsule.

Metformin

Intervention Type: DRUG

Tablet

Part A: Single doses on Day 1 and Day 42 orally

Part B: Subject continues usual metformin dose through Run-in, and resumes after Treatment Period completed

Part C: Subject continues usual metformin dose throughout study

Part A - Placebo

Subjects will titrate up from a maximially tolerated dose over a 7-day period. Treatment Period is 6 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Provided as powder and Capsule.

Part B - Placebo

Subjects will titrate up from a maximially tolerated dose over a 7-day period. Treatment Period is 6 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Provided as powder and Capsule.

Part C - Placebo

Subjects will titrate up from a maximially tolerated dose over a 7-day period. Treatment Period is 6 weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Provided as powder and Capsule.

Interventions

GSK2890457

Provided as powder and capsule.

Intervention Type: DRUG

Metformin

Tablet

Part A: Single doses on Day 1 and Day 42 orally

Part B: Subject continues usual metformin dose through Run-in, and resumes after Treatment Period completed

Part C: Subject continues usual metformin dose throughout study

Intervention Type: DRUG

Placebo

Provided as powder and Capsule.

Intervention Type: DRUG

Liraglutide

Provided as Injection. 6mg/mL, 3mL injector pen that permits doses of 0.6mg, 1.2mg, and 1.8mg

Subcutaneous injection 18 weeks dosing (Stabilization and Treatment Periods, Part B only

Intervention Type: DRUG

Other Intervention Names

Victoza

Eligibility Criteria

Inclusion Criteria

• Subject able to understand and voluntarily provide the consent to participate in the study
• 18 - 70 years of age, inclusive, at the time of signing the informed consent and Body Mass Index (BMI) between 18.0 and 35.0 Kilogram (kg) per m^2, inclusive
• Understands and is willing, able and likely to be compliant with taking study drug and comply with all study procedures and restrictions
• Subject is willing to consume the foods that are part of the standardized breakfast, lunch, and dinner
• In good general health with no clinically significant and relevant abnormalities of medical history or physical examination which includes adequate renal function, alanine transaminase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper Limit of Normal (ULN )
• QTcF < 450 millisecond (msec); or QTcF < 480msec for subjects with right Bundle Branch Block
• Females must be post-menopausal
• Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment
• Females who are > 3 months postpartum and who have undergone a surgical sterilization procedure are eligible to participate in consultation with the GSK Medical Monitor

Parts B and C (Type 2 Diabetic Subjects)

• All the criteria mentioned in Part A except Body Mass Index (BMI) should be between 30.0 and 42.0 kg per m^2
• Diagnosis of T2D for at least 3 months, as defined by the American Diabetes Association
• All T2D subjects must meet label recommendations for metformin
• For Part B, subjects must be willing to discontinue metformin and replace it with daily liraglutide administered by subcutaneous injection and they must meet label recommendations
• No personal history or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2

Exclusion Criteria

• History of gastrointestinal disease, current or chronic history of liver disease, history of serious, severe or unstable physical or psychiatric illness , significant cardiovascular disease, surgery for weight loss or gastrointestinal surgery within 3 months of screening, any documented or reported eating disorder, uncontrolled hypertension, as evidenced by systolic pressure>160 or diastolic pressure >90 mmHg
• Positive test for HIV, Hepatitis B, or Hepatitis C at Screening
• Subjects with significant ECG abnormalities
• For subjects in Part C (continuing metformin), history of untreated pernicious anemia or who have laboratory parameters suggestive of subclinical megaloblastic anemia
• Presence of or symptoms of an active infection
• Uncorrected Thyroid Dysfunction
• History of chronic or acute pancreatitis
• Currently dieting to lose weight including, but not limited to, participation in a program designed to alter body weight within the last 60 days and unwilling to maintain relatively consistent exercise patterns throughout the study
• Current or recent history (within one year of screening) of alcohol or other substance abuse
• Unable to refrain from the use of non-prescription drugs
• Current participation in another clinical study or participation in a clinical study involving an investigational drug within 30 days of the screening visit
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy
• An employee of the sponsor or the study site or members of their immediate family.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Chula Vista, California, United States

GSK Investigational Site

Miami, Florida, United States

GSK Investigational Site

Overland Park, Kansas, United States

Countries

United States

References

Hodge RJ, Paulik MA, Walker A, Boucheron JA, McMullen SL, Gillmor DS, Nunez DJ. Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes. PLoS One. 2016 Apr 19;11(4):e0153151. doi: 10.1371/journal.pone.0153151. eCollection 2016.

Reference Type: DERIVED

PMID: 27093610 (View on PubMed)

Study Documents

Document Type: Annotated Case Report Form

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Clinical Study Report

View Document

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Dataset Specification

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

116623

Identifier Type: -

Identifier Source: org_study_id