A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of AZD9898

NCT03140072 | Terminated Phase 1

• 1 other identifier: D7620C00001
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

In this integrated, multi-part, Phase I study, the safety, tolerability, food effect, pharmacokinetic (PK) and pharmacodynamic (PD) properties of single and repeated doses of AZD9898 will be investigated.

Conditions

Asthma

Keywords

Asthma, Single Ascending Dose (SAD), Multiple Ascending Dose (MAD), AZD9898

Outcome Measures

Primary Outcomes (8)

• Number of patients with Adverse Events (AEs)

  To assess the adverse events as a criteria of safety and tolerability variables.

  Change from baseline up to follow-up (7-10 days after last dose)

• Vital sign (Blood pressure [BP])

  To assess the vital signs as a criteria of safety and tolerability variables.

  Change from baseline up to follow-up (7-10 days after last dose)

• Vital sign (pulse)

  To assess the vital sign as a criteria of safety and tolerability variables.

  Change from baseline up to follow-up (7-10 days after last dose)

• Vital sign (temperature)

  To assess the vital sign as a criteria of safety and tolerability variables.

  Change from baseline up to follow-up (7-10 days after last dose)

• Resting and digital electrocardiograms (ECGs)

  To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.

  Change from baseline up to follow-up (7-10 days after last dose)

• Cardiac telemetry

  To assess the cardiovascular system functioning as a criteria of safety and tolerability variables.

  Change from baseline up to Post-dose (at least 30 minutes pre-dose until at least 24 hours post-dose)

• Physical examination

  To assess the physical conditions as a criteria of safety and tolerability variables.

  Change from baseline up to follow-up (7-10 days after last dose)

• Laboratory assessments (hematology, clinical chemistry and urinalysis)

  To assess hematology, clinical chemistry and urinalysis as a criteria of safety and tolerability variables.

  Change from baseline up to follow-up (7-10 days after last dose)

Secondary Outcomes (21)

• PK assessment: Cmax (Observed maximum plasma concentration taken directly from the individual concentration-time curve)

  Parts 1,2: Days 1,2,3, For Part 3: Days 1, 2, 3,4, 5, 6 and up to Day 12 as needed, 7-13 days post first dose, 8-14 days post first dose

• PK assessment: Ctrough (Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]))

  Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose

• PK assessment: tmax (Time to reach maximum plasma concentration, taken directly from the individual concentration-time curve)

  Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose

• PK assessment: λz (Terminal rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve)

  Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose

• PK assessment: t1/2λz (Terminal half-life, estimated as (ln2)/λz)

  Parts 1,2: At days 1,2,3, For Part 3: At days 1, 2, 3,4, 5, 6 and up to day 12 as needed, 7-13 days post first dose, 8-14 days post first dose

Study Arms (2)

AZD9898

EXPERIMENTAL

In Part 1 of the study, 5 single dose cohorts are planned to be evaluated, where AZD9898 will be administered. Eight subjects will participate in each cohort. Within each cohort, 6 (alternatively 8 or 10) subjects will be randomized to receive a single dose of AZD9898. Fifteen asthma patients are planned to participate in 3 cohorts in Part 2. Five patients will participate in each cohort. Within each cohort, 4 (alternatively 6 or 8) patients will be randomized to receive a single dose of AZD9898. In Part 3, 3 dose cohorts are planned. Nine healthy subjects will participate in each cohort. Within each cohort, 6 (alternatively 8, 10 or 12) subjects will be randomized to receive AZD9898. The subjects taking part in one of the MAD cohorts under fasted conditions will also take part in Part 3B in order to explore the influence of food on the PK of AZD9898.

Drug: AZD9898

Placebo

PLACEBO COMPARATOR

In Part 1 of the study, 5 single dose cohorts are planned to be evaluated, where matching placebo will be administered. Eight subjects will participate in each cohort. Within each cohort, 2 (alternatively 3) subjects will be randomized to receive a single dose of matching placebo. Fifteen asthma patients are planned to participate in 3 cohorts in Part 2. Five patients will participate in each cohort. Within each cohort, one patient (alternatively 2 or 3 patients) will be randomized to receive a single dose of matching placebo. In Part 3, 3 dose cohorts are planned. Nine healthy subjects will participate in each cohort. Within each cohort, 3 (alternatively 4) subjects will be randomized to receive matching placebo.

Drug: Matching Placebo

Interventions

AZD9898 DRUG

In Parts 1 and 2 of the study, each subject/patient will receive a single dose (one dose level) of AZD9898, under fasted conditions. Starting dose in part 1 (SAD in healthy subjects) is 3 mg, subsequent doses will be selected based on emerging data. In Part 3 of the study, each subject will receive one dose level of AZD9898, once daily, under fasted or fed conditions. Subjects participating in Part 3B (food effect cohort) will receive an additional administration of the same dose, on the last day to investigate the effects of food.

AZD9898

Matching Placebo DRUG

In Parts 1 and 2 of the study, each subject/patient will receive a single dose (one dose level) of matching placebo, under fasted conditions. In Part 3 of the study, each subject will receive one dose level of matching placebo, once daily, under fasted or fed conditions. Subjects participating in Part 3B (food effect cohort) will receive an additional administration of the same dose, on the last day to investigate the effects of food.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For Parts 1 and 3:
• Healthy male and female subjects aged 18 to 50 years.
• All females must have a negative pregnancy test at the screening visit and on admission to the clinical unit, must not be lactating and must be of non-childbearing potential. • Has a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• For Part 2:
• Has been diagnosed by a physician with asthma for at least 12 months prior to the screening visit.
• Has an FEV1 ≥ 65% at the screening visit and prior to dosing on Day 1, as measured before administration of a bronchodilator at both time points.
• Has been on stable standard asthma treatment.

You may not qualify if:

• For Parts 1,2,3:
• History of any clinically important disease or disorder.
• History of unstable psychiatric disorders.
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with the drugs.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the screening visit or the first administration of IMP.
• Any clinically important abnormalities in hematology, clinical chemistry or urinalysis results at the screening visit or on admission.
• Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV) type I and II antibodies.
• Abnormal vital signs. Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG.
• Prolonged QTcF \> 450 ms or shortened QTcF \< 340 ms.
• PR (PQ) interval shortening. PR (PQ) interval prolongation.
• Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS \> 110 ms.
• Subjects with QRS \> 110 ms, but \< 115 ms are acceptable if there is no evidence of, e.g., ventricular hypertrophy or pre-excitation.
• Known or suspected history of drug abuse.
• Current smokers or those who have smoked or used nicotine products within the previous 3 months.
• History of alcohol abuse.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (2)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

Research Site

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Muna Albayaty

  PAREXEL Early Phase Clinical Unit London

  PRINCIPAL INVESTIGATOR

• Dave Singh

  The Medicines Evaluation Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 4, 2017
• Study Start: May 10, 2017
• Primary Completion: August 23, 2017
• Study Completion: August 23, 2017
• Last Updated: January 17, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)