To Evaluate the Response to Glucagon During Hypoglycemia

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT00817271

Collaborator

(none)

Enrollment

Location

Arms

1.9

Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the response to Glucagon versus the spontaneous hormonal response to low blood sugar levels in T2DM Patients treated with AZD1656 and Metformin

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: AZD1656 Drug: Glucagon	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomised, Open, Two-Way Cross-Over, Phase I Study to Evaluate the Response to Glucagon Versus the Spontaneous Counter-Regulatory Response in T2DM Patients Treated With AZD1656 and Metformin During Hypoglycemia

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Apr 1, 2009

Actual Study Completion Date :

Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: AZD1656 Dose titration of oral suspension during 2 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose for another 6 days. On day 5 and 8 the dose will be given as a single dose Drug: Glucagon 1 mg injected 3 hr post AZD1656 morning dose on day 5 alt. day 8
Experimental: 2	Drug: AZD1656 Dose titration of oral suspension during 2 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose for another 6 days. On day 5 and 8 the dose will be given as a single dose

Arm

Intervention/Treatment

Experimental: 1

Drug: AZD1656

Dose titration of oral suspension during 2 days to a tolerable dose given twice daily. Subjects will thereafter be treated with this dose for another 6 days. On day 5 and 8 the dose will be given as a single dose

Drug: Glucagon

1 mg injected 3 hr post AZD1656 morning dose on day 5 alt. day 8

Experimental: 2

Drug: AZD1656

Outcome Measures

Primary Outcome Measures

P-Glucose levels [Repeated sampling during the 24 hour period on day 5 and 8]

Secondary Outcome Measures

Safety and tolerability (AE, BP, pulse, plasma glucose, laboratory variables, weight and ECG) [Frequent measurements during the study period]
Pharmacokinetic variables (Area under the plasma conc-time curve from time 0 to 24 hours post dose (AUC0-24), maximum plasma conc(Cmax), time to reach maximum plasma conc(tmax), terminal elimination half-life and apparent oral clearance [Repeated sampling during the 24 hour period on day 5 and 8]
Pharmacodynamics (P-Glucose, S-Insulin and S-C-peptide) [Repeated sampling during the 24 hour period on day 5 and 8]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

type II diabetes patients, female with non child-bearing potential
T2DM diagnosis confirmed by C-peptide >0.3nmol/L and no glutamic acid decarboxylate (GAD) antibodies at enrolment (screening)
Treatment with metformin alone with a total daily dose not less than 1 000 mg. Stable glycaemic control indicated by unchanged treatment within 3 months prior to enrolment

Exclusion Criteria:

History of ischemic heart disease, symptomatic heart failure, stroke, transitory ischemic attack or symptomatic peripheral vascular disease
Signs of diabetic proliferative retinopathy or diabetic maculopathy, at screening or on an ophthalmological examination within 3 months from start of study
Participating in another clinical study during the last 30 days prior to enrolment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Chula Vista	California	United States

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director: Klas Malmberg, MD, PhD, Prof., AstraZeneca R&D Mölndal
Principal Investigator: Marcus Hompesch, MD, Profil Institut for Clinical Research Inc.