Study Of GW823093 In Japanese Subjects With Type 2 Diabetes Mellitus

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00372957
• Other study ID #: DPB106653
• Status: Completed
• Phase: Phase 2
• Start date: March 22, 2006
• Est. completion date: June 28, 2006

Study information

• Verified date: August 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 28, 2006
• Est. primary completion date: June 28, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• GW823093 15mg
White opaque capsule containing 15mg of GW823093 as free base
• GW823093 placebo capsule
Matching placebo of GW823093 capsule or 15mg capsule
• GW823093 30mg
White opaque capsule containing 15mg of GW823093 as free base

Locations

Country	Name	City	State
	GSK Investigational Site

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Up to post-study screen (Follow-up [7 days after the last dose of study medication])