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Study Of GW823093 In Japanese Subjects With Type 2 Diabetes Mellitus

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00372957
First Posted: September 7, 2006
Last Update Posted: October 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
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.

Condition Intervention Phase
Diabetes Mellitus, Type 2 Drug: GW823093 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: PK/PD Study of GW823093 in Japanese Subjects With T2DM: A Single-blind, Placebo Controlled, Randomized, Multi-dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GW823093C Administered Orally for 7 Days in Japanese Subjects With Type 2 Diabetes

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Standard pharmacokinetic (PK) parameter: Maximum observed plasma drug concentration (Cmax) [ Time Frame: 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) ]
    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.

  • Standard PK parameter: Time at which Cmax was observed (Tmax) [ Time Frame: 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) ]
    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.

  • Standard PK parameter: Half life of terminal elimination phase (t1/2) [ Time Frame: 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) ]
    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.

  • 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]) [ Time Frame: 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) ]
    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.

  • Standard PK parameter: Percentage of AUC(0-inf) obtained by extrapolation (%AUCex) [ Time Frame: 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) ]
    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.

  • Standard PK parameter: Constant rate of elimination (lambda_z) [ Time Frame: 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) ]
    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.

  • Standard PK parameter: Total clearance (CL/F) [ Time Frame: 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) ]
    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.

  • Standard PK parameter: Apparent volume of distribution (Vz/F) [ Time Frame: 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) ]
    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.

  • Standard PK parameter: R[Cmax], Extent of accumulation (Ro), Steady state accumulation ratio (Rs) [ Time Frame: 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) ]
    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).

  • Percent Dipeptidyl-peptidase IV (DPP-IV) Inhibition by Dose (Day 7) [ Time Frame: 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.

  • DPP-IV activity weighted mean AUCs at Baseline (Day -1) and Day 7 [ Time Frame: 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).

  • Active Glucagon-like peptide-1 (GLP-1) weighted mean AUCs at Baseline (Day -1) and Day 7 [ Time Frame: 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.

  • Insulin Weighted Mean AUCs at Baseline (Day -1) and Day 7 [ Time Frame: 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.

  • Glucagon Weighted Mean AUCs at Baseline (Day -1) and Day 7 [ Time Frame: 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.

  • C-peptide Weighted Mean AUCs at Baseline (Day -1) and Day 7 [ Time Frame: 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.

  • Glucose Weighted Mean AUCs at Baseline (Day -1) and Day 7 [ Time Frame: 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.


Secondary Outcome Measures:
  • Number of participants with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to post-study screen (Follow-up [7 days after the last dose of study medication]) ]
    AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is serious corresponding to those listed in above definition.


Enrollment: 30
Actual Study Start Date: March 22, 2006
Study Completion Date: June 28, 2006
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • 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.

Exclusion criteria:

  • Must not have any other major illness other than diabetes
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00372957


Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00372957     History of Changes
Other Study ID Numbers: DPB106653
First Submitted: September 5, 2006
First Posted: September 7, 2006
Last Update Posted: October 12, 2017
Last Verified: August 2017

Keywords provided by GlaxoSmithKline:
pharmacodynamics
Diabetes
pharmacokinetics

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases