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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: AZD1446; Drug: AZD1446; Drug: AZD1446; Drug: AZD1446; Drug: AZD1446; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Lulea, Sweden
    • Research Site
  • Uppsala, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 2: Placebo	Drug: Placebo; IR; Drug: Placebo; ER/MR
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; Drug: AZD1446; ER Moderate, 90mg, p.o. capsule; Drug: AZD1446; ER Slow, 90mg, p.o. capsule; Drug: AZD1446; MR; Drug: AZD1446; IR, 90 mg 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 Fast, 90mg, p.o. capsule; Drug: AZD1446; ER Moderate, 90mg, p.o. capsule; Drug: AZD1446; ER Slow, 90mg, p.o. capsule; Drug: AZD1446; MR; Drug: AZD1446; IR, 90 mg 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 Fast, 90mg, p.o. capsule; Drug: AZD1446; ER Moderate, 90mg, p.o. capsule; Drug: AZD1446; ER Slow, 90mg, p.o. capsule; Drug: AZD1446; MR; Drug: AZD1446; IR, 90 mg 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; ER Fast, 90mg, p.o. capsule; Drug: AZD1446; ER Moderate, 90mg, p.o. capsule; Drug: AZD1446; ER Slow, 90mg, p.o. capsule; 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; ER Fast, 90mg, p.o. capsule; Drug: AZD1446; ER Moderate, 90mg, p.o. capsule; Drug: AZD1446; ER Slow, 90mg, p.o. capsule; Drug: AZD1446; MR; Drug: AZD1446; IR, 90 mg p.o. capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Single Dose Administration :• Cmax, tmax, t½λz, AUC0-t, AUC, AUC0-τ (Part 2 only), Frel (Part 1 only), CL/F, Vz/F	Part 1 - 11 days
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)	Part 2 - 10 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1: Single Dose Administration :• Cmax, tmax, t½λz, AUC0-t, AUC, AUC0-τ (Part 2 only), Frel (Part 1 only), CL/F, Vz/F	Part 1 - 11 days
Part 1: Safety and tolerabilty :- Laboratory safety data, vital signs, electrocardiogram, Columbia-Suicide Severity Rating Scale, adverse events, Mini-international neuropsychiatric interview	throughout the approx 7 weeks of study duration
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	Part 2 - 10 days

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Wolfgang Kühn, Quintiles AB, Phase I Services; Study Director: Lena Bolin, AstraZeneca R&D

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: March 10, 2010
• First Submitted That Met QC Criteria: March 23, 2010
• First Posted (Estimate): March 24, 2010

Study Record Updates

• Last Update Posted (Estimate): August 27, 2010
• Last Update Submitted That Met QC Criteria: August 26, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Phase I; healthy volunteers; Pharmacokinetic study; AZD1446; Relative bioavailability
• Other Study ID Numbers: D1950C00008; 2009-017702-36 (EudraCT Number)