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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02367066
• Other study ID #: D6420C00001
• Status: Completed
• Phase: Phase 1
• First received: February 13, 2015
• Last updated: May 26, 2015
• Start date: March 2015
• Est. completion date: May 2015

Study information

• Verified date: May 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• AR-C165395XX
Oral dose of AR-C165395XX (tablets)

Other:
• Placebo
Oral dose of placebo for AR-C165395XX (tablets)

Locations

Country	Name	City	State
United States	Research Site	Chula Vista	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of AR-C165395XX on plasma glucose by assessment of change in glucose concentration-time curve (?AUC-GL0-4h) during MMTT (mixed-meal tolerance test)		Baseline, Day 3 (4 days time frame)	No
Primary	Effect of AR-C165395XX on insulin secretion rate after graded glucose and GLP1 infusion (GGI) by assessment of change in C-peptide concentration-time curve during GGI (?AUC-Cptd 1-2h)		Baseline, Day 2 (3 days time frame)	No
Primary	Effect of AR-C165395XX on plasma glucose by assessment of change in glucose Cmax (?GL-Cmax) during MMTT (mixed-meal tolerance test)		Baseline, Day 3 (4 days time frame)	No
Secondary	Effect of AR-C165395XX on change of plasma insulin after MMTT compared to baseline		Baseline, Day 3 (4 days time frame) at both study periods	No
Secondary	Effect of AR-C165395XX on change in glucose after GGI		Baseline, Day 2 (3 days time frame) at both study periods	No
Secondary	Change in fasting insulin after administration of AR-C165395XX		Baseline, Day 2, Day 3 (4 days time frame) at both study periods	No
Secondary	Pharmacokinetics (PK) of AR-C165395XX will be described as maximum plasma concentration at steady state (Css,max)		Day 2, 3 at both study periods	No
Secondary	Effect of AR-C165395XX on delayed gastric emptying will be measured as change in paracetamol in plasma using maximum concentration in plasma (Cmax) during MMTT		Day 3 at both study periods	No
Secondary	Safety will be described in terms of adverse events, vital signs, electrocardiograms (ECGs), safety laboratory variables	Safety and tolerability after repeated oral doses of AR-C165395XX in T2DM	Enrolment- follow up approx. 8 weeks	Yes
Secondary	Effect of AR-C165395XX on delayed gastric emptying will be measured as change in paracetamol in plasma using Area under the concentration-time curve in plasma from zero (predose) to time of last quantifiable concentration (AUC(0-t)) during MMTT		Day 3 at both study periods	No
Secondary	PK of AR-C165395XX will be described as area under the plasma concentration-time curve during following intervals: 0-1 h (AUC0-1h), 0-2 h (AUC0-2h), 0-4 h (AUC0-4h), 0-12 h (AUC0-12h), 0-24 h (AUC0-24h) and 1-2 h (AUC1-2h)		Day 2, 3 at both study periods	No
Secondary	PK of AR-C165395XX will be described as apparent oral plasma clearance at steady state (CLss/F)		Day 2, 3 at both study periods	No
Secondary	Effect of AR-C165395XX on change of plasma c-peptide after MMTT compared to baseline		Baseline, Day 3 (4 days time frame) at both study periods	No
Secondary	Effect of AR-C165395XX on change of plasma glucagon after MMTT compared to baseline		Baseline, Day 3 (4 days time frame) at both study periods	No
Secondary	Effect of AR-C165395XX on change in insulin after GGI		Baseline, Day 2 (3 days time frame) at both study periods	No
Secondary	Change of beta cell responsiveness after administration of AR-C165395XX		Baseline, Day 2, Days 3 (4 days time frame) at both study periods	No
Secondary	PK of AR-C165395XX will be described as time to steady state Cmax (tss,max)		Day 2, 3 at both study periods	No
Secondary	PK of AR-C165395XX will be described as minimum plasma concentration at steady state (Css,min)		Day 2, 3 at both study periods	No
Secondary	Effect of AR-C165395XX on delayed gastric emptying will be measured as change in paracetamol in plasma using time to Cmax (tmax) during MMTT		Day 3 at both study periods	No