Last updated: 11/07/2018 10:39:49

To investigate the safety, tolerability and pharmacodynamics of GSK2890457 in healthy volunteers and subjects with type 2 diabetes

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GSK study ID
116623
See study documents
Clinicaltrials.gov ID
NCT01725126
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A double-blind [sponsor unblinded], randomized, placebo-controlled, staggered-parallel study to investigate the safety, tolerability, and pharmacodynamics of GSK2890457 in healthy volunteers and subjects with type 2 diabetes
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of participants with any adverse event (AE), serious adverse event (SAE) or death during Part A

Timeframe: Up to Follow-up (8 weeks)

Number of participants with any AE, SAE or death during Part B and Part C

Timeframe: Up to Follow-up (8 weeks)

Number of participants with any hypoglycemic events during Part A

Timeframe: Up to Follow-up (8 weeks)

Number of participants with any hypoglycemic events during Part B and Part C

Timeframe: Up to Follow-up (8 weeks)

Change from Baseline in clinical chemistry parameters of alkaline phosphatase (ALP), ALT, aspartate aminotransferase (AST) and gamma glutamyltransferase (GGT) during double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in clinical chemistry parameters of ALP, ALT, AST and GGT during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in clinical chemistry parameters of electrolytes, glucose phosphorus inorganic and urea/blood urea nitrogen (BUN) during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in clinical chemistry parameters of electrolytes, glucose phosphorus inorganic, BUN and cholesterol during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in clinical chemistry parameters of direct bilirubin, total bilirubin, creatinine and uric acid during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in clinical chemistry parameters of direct bilirubin, total bilirubin, creatinine and uric acid during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in clinical chemistry parameters of albumin and total protein during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in clinical chemistry parameters of albumin and total protein during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in clinical chemistry parameters of insulin during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in clinical chemistry parameters of insulin during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in clinical chemistry parameters of amylase and lipase the double-blind treatment period of Part B of study

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in clinical chemistry parameter of triiodothyronine (T3) uptake during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in clinical chemistry parameters of total thyroxine and total T3 during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in clinical chemistry parameters of thyroid stimulating hormone during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in hematology parameters of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, white blood cell (WBC) count during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in hematology parameters of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count, WBC count during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in hematology parameters of hemoglobin and mean corpuscle hemoglobin concentration (MCHC) during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in hematology parameters of hemoglobin and MCHC during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in hematology parameters of red blood cell (RBC) count and reticulocytes during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in hematology parameters of RBC count and reticulocytes during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in hematology parameter of hematocrit during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in hematology parameter of hematocrit during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in hematology parameter of mean corpuscle hemoglobin (MCH) during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in hematology parameter of MCH during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in hematology parameter of mean corpuscle volume (MCV) during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in hematology parameter of MCV during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Number of participants with abnormal urinalyisis dipstick and microscopic results during the double-blind treatment period of Part A

Timeframe: Up to Day 42

Number of participants with abnormal urinalyisis dipstick and microscopic results during the double-blind treatment period of Part B

Timeframe: Up to Day 42

Number of participants with abnormal urinalyisis dipstick and microscopic results during the double-blind treatment period of Part C

Timeframe: Up to Day 42

Mean specific gravity values of urine during the double-blind treatment period of Part A

Timeframe: Up to Day 42

Mean specific gravity values of urine during the double-blind treatment period of Part B and C

Timeframe: Up to Day 42

Mean pH values of urine during the double-blind treatment period of Part A

Timeframe: up to Day 42

Mean pH values of urine during the double-blind treatment period of Part B and C

Timeframe: Up to Day 42

Change from Baseline in vital sign parameter of systolic blood pressure (SBP) and diastolic blood pressure (DBP) during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in vital sign parameter of SBP and DBP during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in vital sign parameter of heart rate (HR) during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in vital sign parameter of HR during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Day 42

Change from Baseline in Electrocardiogram (ECG) intervals during Part A

Timeframe: Baseline (Day 1, Randomization) up to Follow-up (Day 56)

Change from Baseline in ECG intervals during Part B and C

Timeframe: Baseline (Day -1) up to Follow-up (Day 56)

Change from Baseline in the overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) score during the double-blind treatment period of Part A

Timeframe: Baseline (Day 1, Randomization) up to Day 42

Change from Baseline in the overall GSRS score during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -2) up to Day 41

Change from Baseline in in-clinic body weight during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1 and Day 1) up to Day 42

Percent change from Baseline in in-clinic body weight during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1 and Day 1) up to Day 42

Change from Baseline in weighted mean glucose area under the curves from time 0 to 24 hours (AUC [0-24 hours]) during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in fasting glucose during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42 of Part B and C

Change from Baseline in fasting insulin and weighted mean insulin AUC (0-4 hour) and AUC (0-24 hour) during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in glycated hemoglobin (HbA1c) during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in homeostasis model of assessment–insulin resistance (HOMA-IR]) during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in matsuda index during the double blind-treatment period of Part B and C

Timeframe: Baseline (Day -1) and Day 42

Change from Baseline in fasting plasma glucose (safety laboratory) values during the double-blind treatment period of Part B and C

Timeframe: Baseline (Day -1) up to Follow-up (Day 56)

Secondary outcomes:

Area under plasma concentration from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) of liraglutide during the double-blind treatment period of Part B

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

Maximum observed concentration (Cmax) of liraglutide during the double-blind treatment period of Part B

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

Time of occurrence of Cmax (Tmax) of liraglutide during the double-blind treatment period of Part B

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose

AUC of metformin from time 0 to 10 hours post-dose (AUC [0-10 hour]) during the double-blind treatment period of Part A

Timeframe: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

Cmax of metformin during the double-blind treatment period of Part A

Timeframe: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

Tmax of metformin during the double-blind treatment period of Part A

Timeframe: Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose

AUC from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) of metformin during the double-blind treatment period of Part C

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose

Cmax of metformin during the double-blind treatment period of Part C

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose

Tmax of metformin during the double-blind treatment period of Part C

Timeframe: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose

Interventions:
  • Drug: GSK2890457
  • Drug: Metformin
  • Drug: Placebo
  • Drug: Liraglutide
    • Enrollment:
    53
    Primary completion date:
    2013-12-09
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    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;11(4):e0153151
    Medical condition
    Obesity
    Product
    AH24937, GSK2696326, GSK2851323, GSK2890432, GSK2890457
    Collaborators
    Not applicable
    Study date(s)
    February 2013 to September 2013
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 70 years
    Accepts healthy volunteers
    Yes
    • Part A (Healthy Subjects)
    • Subject able to understand and voluntarily provide the consent to participate in the study
    • 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
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Part A (Healthy Subjects)
    • 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.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Chula Vista, California, United States, 91910
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Overland Park, Kansas, United States, 66211
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Miami, Florida, United States, 33169
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)
    Protocol
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2013-12-09
    Actual study completion date
    2013-12-09

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

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