A Bioavailability Study Comparing Modified-release Capsules and Immediate Release Capsules in Fed and Fasting Conditions - Full Text View

Purpose

Part 1: The purpose of this study is to determine the pharmacokinetic profile of 4 different Extended/modified-release formulations and one immediate release formulation of AZD1446. In addition the food effect on AZD1446 pharmacokinetics will be investigated.

Part 2: To asses the safety and tolerability of the selected formulation(s) from part 1 in elderly healthy volunteers.

Condition	Intervention	Phase
Healthy	Drug: AZD1446 Drug: Placebo	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-availability Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Basic Science
Official Title:	A Phase I Study to Investigate the Relative Bioavailability of Modified-release Formulations of AZD1446 Compared to an Immediate-release Capsule Under Fed and Fasting Conditions Following Single and Repeated Dose Administration to Young and Elderly Healthy Volunteers

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Part 1: Single Dose Administration :• Cmax, tmax, t½λz, AUC0-t, AUC, AUC0-τ (Part 2 only), Frel (Part 1 only), CL/F, Vz/F [ Time Frame: Part 1 - 11 days ] [ Designated as safety issue: No ]
Part 2 Multiple Dose Administration: - Cmax, tmax, t½λz, AUC0-t, AUC, AUC0-τ (Part 2 only), Frel (Part 1 only), CL/F, Vz/F Day 9 of Part 2 following multiple dosing in addition to the above • Cmin, tmin, Cavg, fluctuation ratio, RCmax, RAUC(0-τ) [ Time Frame: Part 2 - 10 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Part 1: Safety and tolerabilty :- Laboratory safety data, vital signs, electrocardiogram, Columbia-Suicide Severity Rating Scale, adverse events, Mini-international neuropsychiatric interview [ Time Frame: throughout the approx 7 weeks of study duration ] [ Designated as safety issue: Yes ]
Part 1: Single Dose Administration :• Cmax, tmax, t½λz, AUC0-t, AUC, AUC0-τ (Part 2 only), Frel (Part 1 only), CL/F, Vz/F [ Time Frame: Part 1 - 11 days ] [ Designated as safety issue: No ]
Part 2 Multiple Dose Administration :- Cmax, tmax, t½λz, AUC0-t, AUC, AUC0-τ (Part 2 only), Frel (Part 1 only), CL/F, Vz/F Day 9 of Part 2 following multiple dosing in addition to the above • Cmin, tmin, Cavg, fluctuation ratio, RCmax, RAUC(0-τ [ Time Frame: Part 2 - 10 days ] [ Designated as safety issue: No ]

Enrollment:	62
Study Start Date:	February 2010
Study Completion Date:	July 2010
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 (2 arms) Period 1: randomized to either fasting IR or ER1. Period 2: Cross-over to either IR or ER1. Period 3: ER1 in fed conditions.	Drug: AZD1446 ER Fast, 90mg, p.o. capsule
Experimental: Cohort 2 (2 arms) Period 1: randomized to either fasting IR or ER2. Period 2: Cross-over to either IR or ER2. Period 3: ER2 in fed conditions.	Drug: AZD1446 ER Moderate, 90mg, p.o. capsule
Experimental: Cohort 3( 2 arms) Period 1: randomized to either fasting IR or ER3. Period 2: Cross-over to either IR or ER3. Period 3: ER3 in fed conditions.	Drug: AZD1446 ER Slow, 90mg, p.o. capsule
Experimental: Cohort 4 (2 arms) Period 1: randomized to either fasting IR or MR4. Period 2: Cross-over to either IR or MR4. Period 3: MR4 in fed conditions.	Drug: AZD1446 MR Drug: AZD1446 IR, 90 mg p.o. capsule
Experimental: Part 2: Extended/Modified release Extended/Modified release capsule to be determined	Drug: AZD1446 MR Drug: AZD1446 IR, 90 mg p.o. capsule
Placebo Comparator: Part 2: Placebo	Drug: Placebo IR Drug: Placebo ER/MR

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Body mass index (BMI) between 19 and 30 kg/m2
Clinically normal findings on physical examination

Exclusion Criteria:

History of any clinically significant disease or disorder
History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
History or present symptoms or signs of severe allergy/hypersensitivity reactions including severe food allergy, as judged by the investigator

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01092299

Locations

Sweden
Research Site
Lulea, Sweden
Research Site
Uppsala, Sweden

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Lena Bolin	AstraZeneca R&D
Principal Investigator:	Aslak Rautio	Quintiles Hermelinen AB
Principal Investigator:	Wolfgang Kühn	Quintiles AB, Phase I Services

More Information

No publications provided

Responsible Party:	MSD, AstraZeneca
ClinicalTrials.gov Identifier:	NCT01092299 History of Changes
Other Study ID Numbers:	D1950C00008, 2009-017702-36
Study First Received:	March 10, 2010
Last Updated:	August 26, 2010
Health Authority:	Sweden: Medical Products Agency

Keywords provided by AstraZeneca:

Phase I
Relative bioavailability
Pharmacokinetic study
AZD1446
healthy volunteers

ClinicalTrials.gov processed this record on May 22, 2013