A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD5718 After Single and Multiple Ascending Dose Administration to Healthy Male Subjects

NCT02632526 | Completed Phase 1 Results

• 1 other identifier: D7550C00001
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, randomised, single-blind, placebo-controlled, first-in-human (FIH) single and multiple ascending dose study consisting of two parts (Part A \[SAD\] and Part B \[MAD\]) to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5718 in healthy male subjects

Conditions

Healthy Male Subjects; Cardiovascular Disease

Keywords

AZD5718 oral suspension crystalline; AZD5718 oral suspension amorphous; Single ascending dose/multiple ascending dose (SAD/MAD); Placebo-controlled; Safety; Tolerability; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability of AZD5718 by Assessment of the Number of Participants With Adverse Events Following Oral Administration of SAD (Part A) and MAD (Part B).

  To assess the safety and tolerability of AZD5718 following oral administration of SAD (Part A) and MAD (Part B).

  From screening to last followup visit (7-10 days after last dose), up to 6 weeks (Part A) and up to 8 weeks (Part B)

Secondary Outcomes (29)

• Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero Extrapolated to Infinity (AUC) for Part A - Amorphous and Crystalline Suspension

  At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)

• Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC) for Part B - Amorphous Suspension

  Day 1 of Part B

• Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve From Time Zero to Time of Last Quantifiable Concentration (AUC(0-last)) for Part A - Amorphous and Crystalline Suspension

  At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)

• Rate and Extent of Absorption of AZD5718 by Assessment of the Area Under the Plasma Concentration-curve Over the Dosing Interval (AUC(0-τ)) for Part B - Amorphous Suspension

  Day 1, Day 9 and Day 10 of Part B

• Rate and Extent of Absorption of AZD5718 by Assessment of the Observed Maximum Plasma Concentration (Cmax) for Part A - Amorphous and Crystalline Suspension

  At post-dose (Days 1 to 3); 0.5, 1, 2, 3, 4, 6, 8, 24, 36 and 48 hours post-dose and folow up (Day 4 - 72 hours post-dose) (Part A only)

Study Arms (17)

AZD5718 amorphous form, treatment 1 (Part A)

EXPERIMENTAL

Starting dose 25 mg/day, single ascending dose

Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous form, treatment 2 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous suspension

Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous form, treatment 3 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous suspension

Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous form, treatment 4 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous suspension

Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous form, treatment 5 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous suspension

Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous form, treatment 6 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous suspension

Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718, crystalline form, treatment 7 (Part A)

EXPERIMENTAL

Crystalline suspension (Part A), dosage lower than highest dose used with amorphous suspension, single ascending dose

Drug: AZD5718 oral suspension crystalline form (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 crystalline form, treatment 8 (Part A)

EXPERIMENTAL

Crystalline suspension (Part A), dosage lower than highest dose used with amorphous suspension, single ascending dose

Drug: AZD5718 oral suspension crystalline form (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous form, treatment 1 (Part B)

EXPERIMENTAL

Once or twice daily from Days 2 to 9 and single doses on Days 1 and 10, dosage TBD (Part A)

Drug: AZD5718 placebo oral suspension; Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B)

AZD5718 amorphous form, treatment 2 (Part B)

EXPERIMENTAL

Once or twice daily from Days 2 to 9 and single doses on Days 1 and 10, dosage TBD (Part A)

Drug: AZD5718 placebo oral suspension; Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B)

AZD5718 amorphous form, treatment 3 (Part B)

EXPERIMENTAL

Once or twice daily from Days 2 to 9 and single doses on Days 1 and 10, dosage TBD (Part A)

Drug: AZD5718 placebo oral suspension; Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B)

AZD5718 amorphous form, treatment 4 (Part B)

EXPERIMENTAL

Once or twice daily from Days 2 to 9 and single doses on Days 1 and 10, dosage TBD (Part A)

Drug: AZD5718 placebo oral suspension; Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B)

AZD5718 amorphous/crystalline form, repeat 1 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous form (Part A) Crystalline form (Part A), dosage lower than highest dose used with amorphous form, single ascending dose

Drug: AZD5718 oral suspension crystalline form (1 to 100 mg/mL) (Part A); Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous/crystalline form, repeat 2 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous form (Part A) Crystalline form (Part A), dosage lower than highest dose used with amorphous form, single ascending dose

Drug: AZD5718 oral suspension crystalline form (1 to 100 mg/mL) (Part A); Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A); Drug: AZD5718 placebo oral suspension

AZD5718 amorphous/crystalline, repeat 3 (Part A)

EXPERIMENTAL

Single dose of AZD5718 amorphous form (Part A) Crystalline form (Part A), dosage lower than highest dose used with amorphous form, single ascending dose

Drug: AZD5718 oral suspension crystalline form (1 to 100 mg/mL) (Part A); Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A)

AZD5718 amorphous form, repeat 1 (Part B)

EXPERIMENTAL

Twice daily dosing (Day 1 - 9) and once daily dosing (Day 10), dosage TBD (Part A)

Drug: AZD5718 placebo oral suspension; Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B)

AZD5718 amorphous form, repeat 2 (Part B)

EXPERIMENTAL

Twice daily dosing (Day 1 - 9) and once daily dosing (Day 10), dosage TBD (Part A)

Drug: AZD5718 placebo oral suspension; Drug: AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B)

Interventions

AZD5718 oral suspension crystalline form (1 to 100 mg/mL) (Part A) DRUG

Oral suspension single dose

AZD5718 amorphous/crystalline form, repeat 1 (Part A); AZD5718 amorphous/crystalline form, repeat 2 (Part A); AZD5718 amorphous/crystalline, repeat 3 (Part A); AZD5718 crystalline form, treatment 8 (Part A); AZD5718, crystalline form, treatment 7 (Part A)

AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part A) DRUG

Single and multiple doses

AZD5718 amorphous form, treatment 1 (Part A); AZD5718 amorphous form, treatment 2 (Part A); AZD5718 amorphous form, treatment 3 (Part A); AZD5718 amorphous form, treatment 4 (Part A); AZD5718 amorphous form, treatment 5 (Part A); AZD5718 amorphous form, treatment 6 (Part A); AZD5718 amorphous/crystalline form, repeat 1 (Part A); AZD5718 amorphous/crystalline form, repeat 2 (Part A); AZD5718 amorphous/crystalline, repeat 3 (Part A)

AZD5718 placebo oral suspension DRUG

Single and multiple doses

AZD5718 amorphous form, repeat 1 (Part B); AZD5718 amorphous form, repeat 2 (Part B); AZD5718 amorphous form, treatment 1 (Part A); AZD5718 amorphous form, treatment 1 (Part B); AZD5718 amorphous form, treatment 2 (Part A); AZD5718 amorphous form, treatment 2 (Part B); AZD5718 amorphous form, treatment 3 (Part A); AZD5718 amorphous form, treatment 3 (Part B); AZD5718 amorphous form, treatment 4 (Part A); AZD5718 amorphous form, treatment 4 (Part B); AZD5718 amorphous form, treatment 5 (Part A); AZD5718 amorphous form, treatment 6 (Part A); AZD5718 amorphous/crystalline form, repeat 1 (Part A); AZD5718 amorphous/crystalline form, repeat 2 (Part A); AZD5718 crystalline form, treatment 8 (Part A); AZD5718, crystalline form, treatment 7 (Part A)

AZD5718 oral suspension amorphous (1 to 100 mg/mL) (Part B) DRUG

Single and multiple doses

AZD5718 amorphous form, repeat 1 (Part B); AZD5718 amorphous form, repeat 2 (Part B); AZD5718 amorphous form, treatment 1 (Part B); AZD5718 amorphous form, treatment 2 (Part B); AZD5718 amorphous form, treatment 3 (Part B); AZD5718 amorphous form, treatment 4 (Part B)

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 - 50 years, inclusive, with suitable veins for cannulation or repeated venepuncture
• 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
• Provision of signed, written and dated informed consent for optional genetic research

You may not qualify if:

• 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 (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 the administration of investigational medicinal product (IMP)
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results at screening and check-in, as judged by the investigator, including:
• Alanine aminotransferase (ALT) \> upper limit of normal (ULN);
• Aspartate aminotransferase (AST) \> ULN;
• Bilirubin (total) \> ULN; and
• Gamma glutamyl transpeptidase (GGT) \> ULN
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV)
• Suspicion or known Gilbert's syndrome
• Abnormal vital signs, after 10 minutes supine rest, at screening and check-in, defined as any of the following:
• Systolic blood pressure(BP) (SBP) \< 90mmHg or ≥ 140 mmHg;
• Diastolic BP (DBP) \< 50mmHg or ≥ 90 mmHg; and
• Pulse \< 45 or \> 85 beats per minute (bpm)
• Any clinically significant abnormalities (at screening and check-in) in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular Diseases

Results Point of Contact

• Title: A study to assess the safety, tolerability, pharmacokinetics & dynamics of AZD5718 in healthy male
• Organization: AstraZeneca AB

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Annelize Koch, MBChB, FFPM

  Parexel

  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: December 7, 2015
• First Posted: December 16, 2015
• Study Start: February 10, 2016
• Primary Completion: August 26, 2016
• Study Completion: August 26, 2016
• Last Updated: March 21, 2019
• Results First Posted: March 21, 2019

Record last verified: 2018-12

Locations

GB (1)