Clinical trial NCT02367066: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: patients
glycaemic control on metformin
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-02-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

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

Primary outcomes:
measure: Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Glucose
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint MMTT C_max for Plasma Glucose
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma C-Peptide
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
Secondary outcomes:
measure: Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma Insulin
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline MMTT AUC(0-4h) for Plasma Glucagon
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint MMTT AUC(0-4h) for Plasma C-Peptide
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Insulin
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Insulin
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma Glucagon
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint GGI AUC(1-2h) for Plasma Glucagon
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint Fasting Beta-cell Responsiveness
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Fasting Insulin at Endpoint
timeFrame: Day 3 and Day 9
measure: Maximum Plasma AZD1981 Concentration at Steady-State, C_ss,Max
timeFrame: Days 2,3,8,9
measure: Time of Maximum Plasma AZD1081 Concentration, t_ss,Max
timeFrame: Days 2,3,8,9
measure: Plasma AZD1981 AUC(0-1h)
timeFrame: Days 2,3,8,9
measure: Plasma AZD1981 AUC(0-2h)
timeFrame: Days 2,3,8,9
measure: Minimum Plasma AZD1981 Concentration at Steady-State, C_ss,Min
timeFrame: Days 2,3,8,9
measure: Plasma AZD1981 AUC(1-2h)
timeFrame: Days 2,3,8,9
measure: Plasma Paracetamol Maximum Concentration, C_max
timeFrame: Days 3,9
measure: Time of Maximum Plasma Paracetamol Concentration, t_max
timeFrame: Days 3,9
measure: Plasma Paracetamol AUC(0-t)
timeFrame: Days 3,9
measure: Change From Baseline to Endpoint GGI AUC(0-1h) for Plasma C-Peptide
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Change From Baseline to Endpoint GGI AUC(0-24h) for Plasma Glucose
timeFrame: Day -1 to Day 3 and Day 6 to Day 9
measure: Plasma AZD1981 AUC(0-4h)
timeFrame: Days 2,3,8,9
measure: Plasma AZD1981 AUC(0-12h)
timeFrame: Days 2,3,8,9
measure: Plasma AZD1981 AUC(0-24h)
timeFrame: Days 2,3,8,9
measure: Apparent Oral Plasma AZD1981 at Steady-State, CL_ss/F
timeFrame: Days 2,3,8,9
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Research Site
state: California
Study officials:
affiliation: Profil Institute for Clinical Research, Inc.
name: Liliana Uribe-Bruce, MD, MCI
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca R&D Mölndal
name: Stanko Skrtic, MD, PhD
role: STUDY_DIRECTOR
References:
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.