Study to Test GSK256073 in Patients With Dyslipidemia

NCT00903617 | Completed Phase 2 Results

• 1 other identifier: 112795
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 11

Brief Summary

This is a two part study (Part A and Part B) that will first aim to establish the PK/PD relationship between exposure and lipid effects (Part A: 75 subjects), and will then confirm the effect using the most relevant dose(s) (Part B: \~90 subjects). Doses of 5mg, 50mg and 150mg of GSK256073 will be administered in Part A, and the dose(s) for Part B will be based on the PK/PD data from Part A. Data from Part A and Part B will be combined to decrease overall subject numbers needed in part B. Part B of the study will include a niaspan arm for relative comparison of the effects of GSK256073 and niacin on lipids and flushing

Conditions

Dyslipidaemias; Dyslipidemias

Keywords

lipids; HM74A

Outcome Measures

Primary Outcomes (1)

• The GSK256073 Area Under Concentration-time Curve (AUC) and High Density Lipoprotein Cholesterol (HDLc) Data to Evolve the Exposure-response Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship for Changes in HDLc Levels

  The potential PK/PD relationship was to be assessed by plotting GSK256073 AUCs against HDLc. The PK/PD model that was to be used for the simulations in the study design was to be refined with the Part A observed AUC exposures and HDLc levels. However, the study was stopped for futility at the end of Part A due to lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising.

  Week 2, 4, 6 and 8

Secondary Outcomes (22)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to follow up (14 days from last dose)

• Number of Participants With Electrocardiography (ECG) Findings

  Up to Week 8

• Change From Baseline in Vital Signs-Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (Week 0) up to Week 8

• Change From Baseline in Vital Signs-Heart Rate

  Baseline (Week 0) up to Week 8

• Number of Participants With Abnormal Hematology Values

  Baseline (Week 0) up to Week 8

Study Arms (8)

Part A Treatment A

EXPERIMENTAL

5 mg of GSK256073

Drug: GSK256073

Part A Treatment B

EXPERIMENTAL

50 mg of GSK256073

Drug: GSK256073

Part A Treatment C

EXPERIMENTAL

150 mg of GSK256073

Drug: GSK256073

Part A Treatment D

PLACEBO COMPARATOR

placebo

Drug: Placebo

Part B Treatment A

PLACEBO COMPARATOR

placebo

Drug: Placebo

Part B Treatment B

ACTIVE COMPARATOR

1500 mg Niaspan

Drug: Niaspan

Part B Treatment C

EXPERIMENTAL

x mg dose of GSK256073 based on data from Part A

Drug: GSK256073

Part B Treatment D

EXPERIMENTAL

optional dose of GSK256073 based on data from Part A

Drug: GSK256073

Interventions

GSK256073 DRUG

5 mg for 8 weeks

Part A Treatment A

Placebo DRUG

placebo for 8 weeks

Part A Treatment D; Part B Treatment A

Niaspan DRUG

1500 mg for 8 weeks

Part B Treatment B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent prior to beginning study-related procedures. 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 18-75 years of age at screening.
• 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.
• Male subjects must agree to use one of several pre-specified contraception methods. This criterion must be followed from the time of the first dose of study medication until three days following the last dose.
• Body weight \> 50 kg (110 pounds) and body mass index (BMI) between 19 and 39 (inclusive)
• LDLc concentration ≥100 mg/dL at screening and within 4 weeks of randomization (if screening occurs \> 4 weeks prior to randomization)
• Fasting triglyceride concentration ≤ 300 mg/dL at screening and within 4 weeks of randomization (if screening occurs \> 4 weeks prior to randomization)
• HDLc ≤ 45 mg/dL for males or ≤ 55 mg/dL for females at screening and within 4 weeks of randomization (if screening occurs \> 4 weeks prior to randomization)
• Subject currently receiving lipid-modifying medication(s) must agree to stop medication(s) for at least 6 weeks prior to randomization. After this washout period LDL, TG and HDL values must be remeasured and meet the above criteria prior to randomization in the study
• AST and ALT \< 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

You may not qualify if:

• Evidence of clinical instability based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter 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 and will not interfere with the study procedures.
• Any change in concomitant medication (including multivitamins, herbal remedies, dietary supplements, and over-the-counter medication) within six weeks prior to screening that is not approved by GSK.
• Any change in diet, exercise habits or smoking status within six weeks prior to screening.
• A medical history significant for the following:
• Clinical cardiovascular disease, including history or current evidence of coronary heart disease, heart failure, cerebrovascular disease, peripheral vascular disease, and/or a 10-year risk of CHD \> 20% while on or titrated off lipid lowering medication. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation.
• Renal impairment (for males) as defined by a calculated GFR \< 60 mL/min . Renal impairment (for females) as defined by a calculated GFR \< 55 ml/min.
• History of diabetes mellitus, or history of post-prandial and/or random blood glucose \> 200 mg/dl or fasting glucose \> 125 mg/dL or currently taking diabetes medications to manage fasting glucose levels (e.g. glitazones, sulfonylureas, insulin, metformin, etc.).
• History of anemia or treatment of anemia within 12 months of screening or Hgb or Hct below the lower limit of reference range for age and gender at screening
• History of pancreatitis
• Any concurrent serious illness (e.g., severe COPD, HIV positive, liver cirrhosis, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject from completing the study
• Active peptic ulcer disease (PUD) and/or history of PUD or other gastrointestinal bleeding within 12 months prior to screening.
• History of kidney stones
• History of gout and/or hyperuricemia or taking drugs for hyperuricemia: allopurinol and/or probenecid
• History of Gilbert's syndrome
• Current inadequately controlled hypertension (blood pressure ≥160 mmHg systolic or ≥100 mmHg diastolic at screening). If blood pressure medication is changed, blood pressure will be re-measured after 6 weeks and must again meet these criteria.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (11)

GSK Investigational Site

Pembroke Pines, Florida, 33026, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46260, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40213, United States

Location

GSK Investigational Site

Auburn, Maine, 04210, United States

Location

GSK Investigational Site

Brooklyn Center, Minnesota, 55430, United States

Location

GSK Investigational Site

Statesville, North Carolina, 28677, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45246, United States

Location

GSK Investigational Site

San Antonio, Texas, 78205, United States

Location

GSK Investigational Site

Richmond, Virginia, 23294, United States

Location

GSK Investigational Site

Olympia, Washington, 98502, United States

Location

GSK Investigational Site

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Olson EJ, Mahar KM, Haws TF, Fossler MJ, Gao F, de Gouville AC, Sprecher DL, Lepore JJ. A Randomized, Placebo-Controlled Trial to Assess the Effects of 8 Weeks of Administration of GSK256073, a Selective GPR109A Agonist, on High-Density Lipoprotein Cholesterol in Subjects With Dyslipidemia. Clin Pharmacol Drug Dev. 2019 Oct;8(7):871-883. doi: 10.1002/cpdd.704. Epub 2019 Jul 3.

  PMID: 31268250 BACKGROUND

MeSH Terms

Conditions

Dyslipidemias

Interventions

8-chloro-3-pentyl-1H-purine-2,6(3H,7H)-dione; Niacin

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The study was stopped for futility at the end of Part A due to lack of a compelling PK/PD relationship between GSK256073 and lipid effects that would predict success in achieving significant HDLc raising.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2009
• First Posted: May 18, 2009
• Study Start: June 15, 2009
• Primary Completion: February 16, 2010
• Study Completion: February 16, 2010
• Last Updated: December 5, 2019
• Results First Posted: September 21, 2017

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (11)