Clinical trial NCT00977626: Study to Investigate Safety, Tolerability and Pharmacokinetics of AZD2423 Multiple Doses in Healthy Volunteers
Official title: A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral AZD2423 Solution After Multiple Ascending Doses in Young and Elderly Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Safety
Tolerability
Healthy
Pharmacokinetics
Healthy volunteers
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-09-16
Enrollment: 74
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Three-part study investigating the safety and tolerability of AZD2423 multiple doses in 98 healthy volunteers: Part 1 80 young and elderly subjects in a parallel, double blind, randomised study. Part 2 - 6 subjects in an open, non-randomised study. Part 3 - 12 subjects in a three-way cross over, open label, partially randomised study.

Part 1 has 2 Arms, AZD2423 or Placebo, Multiple dosing during 10-14 days . Part 2 has 1 Arm AZD2423 Multiple dosing and Part 3 has 3 Arms AZD2423 single dosing or AZD2423 single dosing with food or AZD2423 single dosing, Fasting Condition


Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated, written informed consent prior to any study specific procedures
* Healthy male and non-fertile female subjects aged ≥20 to ≤55 years inclusive and healthy male and female subjects aged ≥65 to ≤80 years inclusive with suitable veins for cannulation or repeated venepuncture.
* Have a body mass index (BMI) between ≥18 and ≤30 kg/m2, as calculated by the investigator, and weigh at least 50 kg and no more than 100 kg.
* Clinically normal physical findings including supine blood pressure, pulse rate, ECG, and laboratory assessments in relation to age, as judged by the investigator. In addition, normal ophthalmoscopy is required for the CSF panel subjects (Part 2).

Exclusion Criteria:

* History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study,or influence the results or the subject's ability to participate in the study
* History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs.
* Any clinically significant illness/infection or medical/surgical procedure or trauma, as judged by the Principal Investigator, within 3 months of the first administration of investigational product.

Primary outcomes:
measure: Investigate the safety and tolerability of AZD2423 in young and elderly subjects following multiple ascending doses at steady state and, if possible, estimate the maximum tolerated dose if within the predefined exposure limits (Part 1 and 2 only).
timeFrame: Part 1:Safety samples taken frequently throughout the study at screening, d-1 and from days 2-16 and at the follow up visit. Part 2: Safety samples taken frequently throughout the study at screening, d-1 and from days 1-9 and at follow up visit.
Secondary outcomes:
measure: Characterize multiple dose PK of AZD2423 and assess time required to reach steady state, degree of accumulation and time dependency of PK (Part 1 and Part 2 only). Characterize single and multiple dose PK of AZD2423 in elderly subjects (Part 1 only)
timeFrame: Part 1: PK will be taken days 1-14 inclusive and at follow-up, with a full PK day on Day 1 and 14. Part 2: PK samples taken on days 1-9 and at follow up visit. Day 1 and 8 is a full PK day.
measure: To investigate concentration of AZD2423 in cerebrospinal fluid (CSF) (Part 2 only).
timeFrame: Part 2: CSF Samples will be taken on day 8 at 4 and 24 hours post dose.
measure: Investigate the PK of tablet formulation compared to oral solution, effect of food compared to fasting, and investigate the safety and tolerability of oral solution and tablet formulation of AZD2423 in young subjects after admin. of single dose (Part 3)
timeFrame: Safety samples taken frequently throughout the study at screening, d-1 and from days 2+3 7-10, 14, 16+17 and at the follow up visit. PK samples will be taken on days 1-4, 8-11, 15-18 and at the follow up visit.
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
affiliation: PAREXEL Early Phase Clinical Uniit, London
name: Dr Muna Albayaty
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca R&D
name: Richard Malamut
role: STUDY_DIRECTOR
References: