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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: AR-C165395XX
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Provision of informed consent Male or female of non-childbearing potential (postmenopausal, and/or have undergone hysterectomy and/or bilateral oophorectomy or salpingectomy/tubal ligation) aged ≥18. Patients with HbA1c ≥7.5 but ≤11% at enrolment visit (Visit 1) ody mass index >19 to <38 kg/m2 he fasting plasma glucose should be in the range of 3-14 mmol/L (54-252 mg/dL, nclusive) on the morning of Visit 1. Clinical diagnosis of type 2 diabetes mellitus Metformin as only anti-diabetic treatment, at least for the last 3 months 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AR-C165395XX + placebo<br>1st period AR-C165395XX 2nd period placebo | Drug: AR-C165395XX<br>* Oral dose of AR-C165395XX (tablets)<br>|
| Placebo Comparator: Placebo + AR-C165395XX<br>1st period Placebo for AR-C165395XX 2nd period AR-C165395XX | Other: Placebo<br>* Oral dose of placebo for AR-C165395XX (tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose | MMTT=Mixed Meal Tolerance Test AUC=Area Under Curve | Day -1 to Day 3 and Day 6 to Day 9 | 
| 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 | GGI=Glucose and GLP1 infusion AUC=Area Under Curve | Day -1 to Day 3 and Day 6 to Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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patients, glycaemic control on metformin