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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: AZD1446
* Drug: AZD1446
* Drug: AZD1446
* Drug: AZD1446
* Drug: AZD1446
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (2 arms)<br>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<br>* ER Fast, 90mg, p.o. capsule<br>|
| Experimental: Cohort 2 (2 arms)<br>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<br>* ER Moderate, 90mg, p.o. capsule<br>|
| Experimental: Cohort 3( 2 arms)<br>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<br>* ER Slow, 90mg, p.o. capsule<br>|
| Experimental: Cohort 4 (2 arms)<br>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<br>* MR<br>Drug: AZD1446<br>* IR, 90 mg p.o. capsule<br>|
| Experimental: Part 2: Extended/Modified release<br>Extended/Modified release capsule to be determined | Drug: AZD1446<br>* MR<br>Drug: AZD1446<br>* IR, 90 mg p.o. capsule<br>|
| Placebo Comparator: Part 2: Placebo<br> | Drug: Placebo<br>* IR<br>Drug: Placebo<br>* ER/MR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Relative bioavailability, Pharmacokinetic study, AZD1446, healthy volunteers