A Phase I, Randomized, Single-blind, Placebo-controlled Study to Access the Safety, Tolerability and Pharmacokinetics of AZD9977 Following Single Ascending Dose Administration to Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- AZD9977, oral suspension
- Conditions
- Safety
- Sponsor
- AstraZeneca
- Enrollment
- 196
- Locations
- 1
- Primary Endpoint
- Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Detailed Description
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 with oral solution as reference. The study will be performed at a single study centre.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
AZD9977 oral suspension, single doses
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
Intervention: AZD9977, oral suspension
Placebo, oral suspension, single doses
In Part A up to 10 cohorts with single doses with matching placebo to AZD9977
Intervention: Placebo, oral suspension
AZD9977, oral solution, single dose
In Part B, of oral solution of AZD9977 will be used as reference
Intervention: AZD9977, oral solution
Outcomes
Primary Outcomes
Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry
Time Frame: For up to 4 days, i.e. on the day before each dosing and for 24 hours after each dosing
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events
Time Frame: For up to 45 days, i.e. from Screening to Follow-up
To assess the safety and tolerability of single ascending doses of AZD9977
Secondary Outcomes
- 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)
- Apparent Clearance (CL/F)(Pre-dose and post-dose upto 48 hrs)
- Apparent Volume of Distribution (Vz/F)(Pre-dose and post-dose upto 48 hrs)
- Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)](Pre-dose and post-dose upto 48 hrs)
- Fraction Excreted Unchanged in Urine[Fe (0-48)](Pre-dose and post-dose upto 48 hrs)
- Renal Clearance of Drug From Plasma [CLR (0-48)](Pre-dose and post-dose upto 48 hrs)