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

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AR-C165395XX
Placebo
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring patients, glycaemic control on metformin

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AR-C165395XX + placebo

Placebo + AR-C165395XX

Arm Description

1st period AR-C165395XX 2nd period placebo

1st period Placebo for AR-C165395XX 2nd period AR-C165395XX

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
February 13, 2015
Last Updated
May 17, 2016
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02367066
Brief Title
A Phase I Study to Assess the Pharmacodynamics of Oral AR-C165395XX in Subjects With Type 2 Diabetes Mellitus (T2DM)
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
patients, glycaemic control on metformin

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AR-C165395XX + placebo
Arm Type
Experimental
Arm Description
1st period AR-C165395XX 2nd period placebo
Arm Title
Placebo + AR-C165395XX
Arm Type
Placebo Comparator
Arm Description
1st period Placebo for AR-C165395XX 2nd period AR-C165395XX
Intervention Type
Drug
Intervention Name(s)
AR-C165395XX
Intervention Description
Oral dose of AR-C165395XX (tablets)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Oral dose of placebo for AR-C165395XX (tablets)
Primary Outcome Measure Information:
Title
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose
Description
MMTT=Mixed Meal Tolerance Test AUC=Area Under Curve
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint MMTT C_max for Plasma Glucose
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide
Description
GGI=Glucose and GLP1 infusion AUC=Area Under Curve
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Secondary Outcome Measure Information:
Title
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint Fasting Beta-cell Responsiveness
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Fasting Insulin at Endpoint
Time Frame
Day 3 and Day 9
Title
Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max
Time Frame
Days 2,3,8,9
Title
Time of Maximum Plasma AZD1081 Concentration, t_ss,Max
Time Frame
Days 2,3,8,9
Title
Plasma AZD1981 AUC(0-1h)
Time Frame
Days 2,3,8,9
Title
Plasma AZD1981 AUC(0-2h)
Time Frame
Days 2,3,8,9
Title
Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min
Time Frame
Days 2,3,8,9
Title
Plasma AZD1981 AUC(1-2h)
Time Frame
Days 2,3,8,9
Title
Plasma Paracetamol Maximum Concentration, C_max
Time Frame
Days 3,9
Title
Time of Maximum Plasma Paracetamol Concentration, t_max
Time Frame
Days 3,9
Title
Plasma Paracetamol AUC(0-t)
Time Frame
Days 3,9
Title
Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose
Time Frame
Day -1 to Day 3 and Day 6 to Day 9
Title
Plasma AZD1981 AUC(0-4h)
Time Frame
Days 2,3,8,9
Title
Plasma AZD1981 AUC(0-12h)
Time Frame
Days 2,3,8,9
Title
Plasma AZD1981 AUC(0-24h)
Time Frame
Days 2,3,8,9
Title
Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F
Time Frame
Days 2,3,8,9

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liliana Uribe-Bruce, MD, MCI
Organizational Affiliation
Profil Institute for Clinical Research, Inc.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stanko Skrtic, MD, PhD
Organizational Affiliation
AstraZeneca R&D Mölndal
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Chula Vista
State/Province
California
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30557325
Citation
Skrtic S, Tyrberg B, Broberg M, Ericsson H, Schnecke V, Kjaer M, Hompesch M, Andersson EM, Ryberg E, Aivazidis A, Wennberg Huldt C, Lofgren L, Morrow L, Parkinson J, Ryden-Bergsten T, Watkins E, Sorhede Winzell M. Exploring the insulin secretory properties of the PGD2-GPR44/DP2 axis in vitro and in a randomized phase-1 trial of type 2 diabetes patients. PLoS One. 2018 Dec 17;13(12):e0208998. doi: 10.1371/journal.pone.0208998. eCollection 2018.
Results Reference
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A Phase I Study to Assess the Pharmacodynamics of Oral AR-C165395XX in Subjects With Type 2 Diabetes Mellitus (T2DM)

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