A Phase I Study to Assess the Pharmacodynamics of Oral AR-C165395XX in Subjects With Type 2 Diabetes Mellitus (T2DM)

Phase 1

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: AR-C165395XX
Other: Placebo

Registration Number: NCT02367066

Lead Sponsor: AstraZeneca

Brief Summary: A study to assess the Pharmacodynamics of oral AR-C165395XX after Administration of Repeated Doses for 3 days in Subjects with Type 2 Diabetes Mellitus

Detailed Description: A Single Centre, Double-blind, Randomised, Placebo-controlled, Cross-over Phase I Study to Assess the Pharmacodynamics of oral AR-C165395XX after Administration of Repeated Doses for 3 days in Subjects with Type 2 Diabetes Mellitus

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

History or sign of any clinically significant disease or disorder which, in the opinion f the investigator, may either put the subject at risk because of participation in the sudy, or influence the results or the subject's ability to participate in the study
Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) laboratory results >3x upper level of normal range (ULN) Clinical diagnosis of Type 1 diabetes mellitus and/or history of diabetic ketoacidosis or positive Glutamic Acid Decarboxylase Autoantibodies test (GAD antibodies test).
Patients treated with single Insulin therapy within the last 3 months

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
AR-C165395XX + placebo	AR-C165395XX	1st period AR-C165395XX 2nd period placebo
Placebo + AR-C165395XX	Placebo	1st period Placebo for AR-C165395XX 2nd period AR-C165395XX

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose	Day -1 to Day 3 and Day 6 to Day 9	MMTT=Mixed Meal Tolerance Test AUC=Area Under Curve
Change From Baseline to Endpoint MMTT C_max for Plasma Glucose	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide	Day -1 to Day 3 and Day 6 to Day 9	GGI=Glucose and GLP1 infusion AUC=Area Under Curve

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint Fasting Beta-cell Responsiveness	Day -1 to Day 3 and Day 6 to Day 9
Fasting Insulin at Endpoint	Day 3 and Day 9
Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max	Days 2,3,8,9
Time of Maximum Plasma AZD1081 Concentration, t_ss,Max	Days 2,3,8,9
Plasma AZD1981 AUC(0-1h)	Days 2,3,8,9
Plasma AZD1981 AUC(0-2h)	Days 2,3,8,9
Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min	Days 2,3,8,9
Plasma AZD1981 AUC(1-2h)	Days 2,3,8,9
Plasma Paracetamol Maximum Concentration, C_max	Days 3,9
Time of Maximum Plasma Paracetamol Concentration, t_max	Days 3,9
Plasma Paracetamol AUC(0-t)	Days 3,9
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide	Day -1 to Day 3 and Day 6 to Day 9
Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose	Day -1 to Day 3 and Day 6 to Day 9
Plasma AZD1981 AUC(0-4h)	Days 2,3,8,9
Plasma AZD1981 AUC(0-12h)	Days 2,3,8,9
Plasma AZD1981 AUC(0-24h)	Days 2,3,8,9
Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F	Days 2,3,8,9