Study Of GW823093 In Japanese Subjects With Type 2 Diabetes Mellitus

NCT00372957 | Completed Phase 2 Results

• 1 other identifier: DPB106653
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

To investigate the preliminary pharmacokinetics, pharmacodynamics, safety and tolerability of GW823093 at doses of 15mg and 30mg given once daily for 7 days in Japanese Type 2 diabetes mellitus (T2DM) patients.

Conditions

Diabetes Mellitus, Type 2

Keywords

pharmacodynamics; Diabetes; pharmacokinetics

Outcome Measures

Primary Outcomes (16)

• Standard Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Drug Concentration (Cmax)

  PK parameters were calculated using data at the actual time of blood collection. Cmax was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hours [hr]), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: Time at Which Cmax Was Observed (Tmax)

  PK parameters were calculated using data at the actual time of blood collection. Tmax was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: Half Life of Terminal Elimination Phase (t1/2)

  PK parameters were calculated using data at the actual time of blood collection. T1/2 was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: Area Under the Plasma Drug Concentration Versus Time Curve Extrapolated to Infinity (AUC[0-inf]), AUC From 0 to the Last Measurable Concentration (AUC[0-t])

  PK parameters were calculated using data at the actual time of blood collection. AUC\[0-inf\] and AUC\[0-t\] was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: Percentage of AUC(0-inf) Obtained by Extrapolation (%AUCex)

  PK parameters were calculated using data at the actual time of blood collection. %AUCex was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: Constant Rate of Elimination (lambda_z)

  PK parameters were calculated using data at the actual time of blood collection. Lambda\_z was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: Total Clearance (CL/F)

  PK parameters were calculated using data at the actual time of blood collection. CL/F was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: Apparent Volume of Distribution (Vz/F)

  PK parameters were calculated using data at the actual time of blood collection. Vz/F was determined from plasma concentration-time data, using standard model independent methods.

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Standard PK Parameter: R[Cmax], Extent of Accumulation (Ro), Steady State Accumulation Ratio (Rs)

  PK parameters were calculated using data at the actual time of blood collection. R\[Cmax\], Ro and Rs were determined from plasma concentration-time data, using standard model independent methods. R\[Cmax\] = Cmax (Day 7)/Cmax (Day 1), Ro = AUC(0-tau) (Day 7)/ AUC(0-tau) (Day 1) and Rs = AUC(0-tau) (Day 7)/ AUC(0-inf) (Day 1).

  Day 1 (at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 hr), Day 2 (0 hr) and Day 7 (0, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hr)

• Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7)

  For analysis of DPP-IV activity, approximately 2 mL of whole blood was collected into a vacuum tube containing ethylenediamine tetraacetic acid (EDTA2K) and centrifuged at approximately 4 degree Celsius, at approximately 2500 revolution per minute (rpm) for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. DPP-IV inhibition was estimated by using the percent change from pre-dose of DPP-IV activity. DPP-IV inhibition was done at pre-dose, 0.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr and 24 hr.

  Day 7

• DPP-IV Activity Weighted Mean AUCs at Baseline (Day -1) and Day 7

  For analysis of DPP-IV activity, approximately 2 mL of whole blood was collected into a vacuum tube containing EDTA2K and centrifuged at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis has been presented in analysis. Unit of measure: Nano mole per minute per milliliter (nmol/min/mL).

  Baseline (Day -1) and Day 7

• Active Glucagon-like Peptide-1 (GLP-1) Weighted Mean AUCs at Baseline (Day -1) and Day 7

  For the analysis of active GLP-1 concentrations, approximately 3 mL of whole blood was collected into a vacuum tube containing DPP-IV inhibitor, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

  Baseline (Day -1) and Day 7

• Insulin Weighted Mean AUCs at Baseline (Day -1) and Day 7

  For the analysis of plasma insulin, approximately 2 mL of whole blood was collected into a vacuum tube containing EDTA2Na, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

  Baseline (Day -1) and Day 7

• Glucagon Weighted Mean AUCs at Baseline (Day -1) and Day 7

  For the analysis of plasma glucagons concentrations, approximately 2 mL of whole blood was collected into a vacuum tube containing aprotinin, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

  Baseline (Day -1) and Day 7

• C-peptide Weighted Mean AUCs at Baseline (Day -1) and Day 7

  For the analysis of plasma C-peptide concentrations, approximately 2 mL of whole blood was collected into a vacuum tube containing EDTA2Na, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

  Baseline (Day -1) and Day 7

• Glucose Weighted Mean AUCs at Baseline (Day -1) and Day 7

  For the analysis of plasma glucose concentrations, approximately 2 mL of whole blood was collected into a vacuum tube containing sodium fluoride, and then centrifuged in a refrigerated centrifuge at approximately 4 degree Celsius, at approximately 2500 rpm for 15 minutes. Samples were stored in a freezer at -70 degree Celsius or lower. Double-delta represented the active treatment within participant change from Baseline summarized across participants, subtracted from placebo within participant change from Baseline summarized across participants. AUC with respect to these time interval was calculated using linear trapezoidal rule by sum of the areas between each chronological pair of assessments (using observed times). Weighted mean was then determined by dividing AUC by observed length of collection interval (time of last assessment - time of first assessment in hr). Double-delta analysis for weighted mean AUCs has been presented in the statistical analysis section.

  Baseline (Day -1) and Day 7

Secondary Outcomes (1)

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

  Up to post-study screen (Follow-up [7 days after the last dose of study medication])

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants received two capsules of matching placebo orally once daily in the morning with 150 milliliter (mL) of water at least 15 minutes prior to breakfast for 7 Days.

Drug: GW823093 placebo capsule

GW823093C 15 mg

EXPERIMENTAL

Participants received one 15 milligrams (mg) of GW823093C capsule and one placebo capsule orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.

Drug: GW823093 15mg; Drug: GW823093 placebo capsule

GW823093C 30 mg

EXPERIMENTAL

Participants received 30 mg (2x15 mg) of GW823093C capsules orally once daily in the morning with 150 mL of water at least 15 minutes prior to breakfast for 7 Days.

Drug: GW823093 30mg

Interventions

GW823093 15mg DRUG

White opaque capsule containing 15mg of GW823093 as free base

Also known as: GW823093

GW823093C 15 mg

GW823093 placebo capsule DRUG

Matching placebo of GW823093 capsule or 15mg capsule

GW823093C 15 mg; Placebo

GW823093 30mg DRUG

White opaque capsule containing 15mg of GW823093 as free base

GW823093C 30 mg

Eligibility Criteria

• Age: 20 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• T2DM diagnosed at least 3 months prior to Screening and fasting plasma glucose (FPG) level \<280mg/dL at the Screening visit.
• Concurrent T2DM therapy: Must be diet controlled - OR - not taking more than 2 oral anti-diabetic agents, and willing to withdraw from these treatments 2 weeks prior to the first dosing.

You may not qualify if:

• Must not have any other major illness other than diabetes

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Condition Hierarchy (Ancestors)

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

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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2006
• First Posted: September 7, 2006
• Study Start: March 22, 2006
• Primary Completion: June 28, 2006
• Study Completion: June 28, 2006
• Last Updated: September 4, 2018
• Results First Posted: March 19, 2018

Record last verified: 2018-08