A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 After Single Ascending Doses to Healthy Males

NCT02484729 | Completed Phase 1 Results

• 2 other identifiers: D6400C000012015-000877-11
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be a randomized, single-blind, placebo-controlled first-in-human study in healthy male subjects to assess the safety, tolerability and pharmacokinetics of single ascending doses of AZD9977. In Part B of this study the regional absorption of AZD9977 along the gastro-intestinal tract will be investigated using the IntelliCap® system in a non-randomized, open-label, fixed-sequence design. The study will be performed at a single study centre.

Conditions

Safety; Tolerability; Pharmacokinetics; Healthy Subjects

Keywords

AZD9977; Safety; Tolerability; Pharmacokinetics; First-in-human; Single Ascending Dose; Regional absorption; Healthy male subjects

Outcome Measures

Primary Outcomes (9)

• Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

• Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

• Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

• Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 4 days, i.e. on the day before each dosing and for 24 hours after each dosing

• Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

• Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

• Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

• Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

• Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis

  To assess the safety and tolerability of single ascending doses of AZD9977

  For up to 45 days, i.e. from Screening to Follow-up

Secondary Outcomes (10)

• Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity.

  Pre-dose and post-dose upto 48 hrs

• Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t)

  Pre-dose and post-dose upto 48 hrs

• Observed Maximum Concentration (Cmax)

  Pre-dose and post-dose upto 48 hrs

• Time to Maximum Observed Plasma Concentration (t Max)

  Pre-dose and post-dose upto 48 hrs

• Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz)

  Pre-dose and post-dose upto 48 hrs

Study Arms (3)

AZD9977 oral suspension, single doses

EXPERIMENTAL

In Part A up to 10 cohorts with single ascending doses with AZD9977 as oral suspension. In Part B AZD9977 as oral suspension in IntelliCap® capsule

Drug: AZD9977, oral suspension

Placebo, oral suspension, single doses

PLACEBO COMPARATOR

In Part A up to 10 cohorts with single doses with matching placebo to AZD9977

Drug: Placebo, oral suspension

AZD9977, oral solution, single dose

EXPERIMENTAL

In Part B, of oral solution of AZD9977 will be used as reference

Drug: AZD9977, oral solution

Interventions

AZD9977, oral suspension DRUG

Single ascending doses of AZD9977 oral suspension (Part A) Single dose of AZD9977 oral suspension in IntelliCap® capsule in regional absorption part (Part B)

AZD9977 oral suspension, single doses

Placebo, oral suspension DRUG

Matching placebo

Placebo, oral suspension, single doses

AZD9977, oral solution DRUG

AZD9977, single dose of oral solution in Part B as reference

AZD9977, oral solution, single dose

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated written informed consent prior to any study specific procedures.
• Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture.
• Male subjects have to comply with the restrictions for sexual activity provided to them.
• Have 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.
• Optional: Provision of signed and dated written informed consent for genetic research.
• If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
• Able to understand, read and speak the English language.

You may not qualify if:

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study.
• History or presence of GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of dosing in Part A or the first dose of AZD9977 in Part B.
• Any clinically significant abnormalities in hematology, clinical chemistry or urinalysis results, as judged by the investigator.
• Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibodies.
• Abnormal findings in vital signs, after 10 minutes resting in the supine position, defined as any of the following:
• Systolic blood pressure (SBP) \< 90 mmHg or ≥ 140 mmHg
• Diastolic blood pressure (DBP) \< 50 mmHg or ≥ 90 mmHg
• Pulse \< 45 or \> 90 bpm
• Any clinically important abnormalities in rhythm, conduction or morphology of the electrocardiogram (ECG) at screening or pre-dose, as considered by the investigator.
• Prolonged QTcF \> 450 ms or family history of long QT syndrome.
• PR (PQ) interval shortening \< 120 ms. PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre-excitation.
• PR (PQ) interval prolongation \> 240ms; intermittent second or third degree atrioventricular (AV) block, or AV dissociation.
• Wenckebach block while asleep is not exclusive.
• Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS \> 110 ms.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, United Kingdom

Location

MeSH Terms

Interventions

AZD9977; Suspensions

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Global Clinical Leader
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

+46 31 7761000

Study Officials

• Muna Albayaty, Dr.

  PAREXEL Early Phase Clinical Unit London, Level 7, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2015
• First Posted: June 30, 2015
• Study Start: July 1, 2015
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 28, 2017
• Results First Posted: March 24, 2017

Record last verified: 2017-03

Locations

GB (1)