NCT02532998

Brief Summary

This is a Phase I, Randomized, Single-Blind, Crossover Study to Assess the Pharmacodynamics of AZD9977 following Single-Dose administration to healthy male subjects

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Sep 2015

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 26, 2015

Completed
6 days until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
3 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

March 29, 2017

Completed
Last Updated

March 29, 2017

Status Verified

February 1, 2017

Enrollment Period

3 months

First QC Date

August 24, 2015

Results QC Date

December 1, 2016

Last Update Submit

February 9, 2017

Conditions

PharmacodynamicsHealthy Subjects

Keywords

PharmacodynamicsAZD9977SafetyTolerabilityPharmacokineticsEplerenoneFludrocortisone

Outcome Measures

Primary Outcomes (1)

  • Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977.

    The sum over the urine collection intervals of the logarithm of the urinary sodium/potassium ratio from two hours to eight hours post-dose. NOTE: Data are presented as the sum of the difference between ln(Na+) and ln(K+) over the collected intervals 2-4, 4-6 and 6-8 hours.

    From 2 hours post dose to 8 hours post dose

Secondary Outcomes (26)

  • Observed Maximum Concentration (Cmax) of AZD9977

    From 2 hours post dose to 8 hours post dose

  • Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977.

    From 2 hours post dose to 8 hours post dose

  • Area Under the Plasma Concentration-time Curve From Time Zero to t Hours After Dosing (AUC[0-t]) of AZD9977.

    From 2 hours post dose to 8 hours post dose

  • Time to Reach Maximum Concentration (Tmax) of AZD9977.

    From 2 hours post dose to 8 hours post dose

  • Terminal Half-life (t½λz) of AZD9977.

    From 2 hours post dose to 8 hours post dose

  • +21 more secondary outcomes

Study Arms (8)

Treatment Sequence 1

EXPERIMENTAL

Period 1: fludrocortisone + eplerenone + AZD9977 Period 2: fludrocortisone + eplerenone + AZD9977 Placebo Period 3: fludrocortisone + AZD9977 Placebo Period 4: fludrocortisone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Treatment Sequence 2

EXPERIMENTAL

Period 1: fludrocortisone + AZD9977 Placebo Period 2: fludrocortisone + eplerenone + AZD9977 Period 3: fludrocortisone + AZD9977 Period 4: fludrocortisone + eplerenone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Treatment Sequence 3

EXPERIMENTAL

Period 1: fludrocortisone + AZD9977 Period 2: fludrocortisone + AZD9977 Placebo Period 3: fludrocortisone + eplerenone + AZD9977 Placebo Period 4: fludrocortisone + eplerenone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Treatment Sequence 4

EXPERIMENTAL

Period 1: fludrocortisone + eplerenone + AZD9977 Placebo Period 2: fludrocortisone + eplerenone + AZD9977 Period 3: fludrocortisone + AZD9977 Period 4: fludrocortisone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Treatment Sequence 5

EXPERIMENTAL

Period 1: fludrocortisone + eplerenone + AZD9977 Period 2: fludrocortisone + eplerenone + AZD9977 Placebo Period 3: fludrocortisone + AZD9977 Placebo Period 4: fludrocortisone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Treatment Sequence 6

EXPERIMENTAL

Period 1: fludrocortisone + AZD9977 Placebo Period 2: fludrocortisone + eplerenone + AZD9977 Period 3: fludrocortisone + AZD9977 Period 4: fludrocortisone + eplerenone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Treatment Sequence 7

EXPERIMENTAL

Period 1: fludrocortisone + AZD9977 Period 2: fludrocortisone + AZD9977 Placebo Period 3: fludrocortisone + eplerenone + AZD9977 Placebo Period 4: fludrocortisone + eplerenone + AZD9977 Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Treatment Sequence 8

EXPERIMENTAL

Period 1: fludrocortisone + eplerenone + AZD9977 Placebo Period 2: fludrocortisone + AZD9977 Period 3: fludrocortisone + eplerenone + AZD9977 Period 4: fludrocortisone + AZD9977 Placebo Period 5: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment Period 6: fludrocortisone + eplerenone and/or AZD9977 or AZD9977 Placebo treatment

Drug: AZD9977 oral suspensionDrug: AZD9977 placebo oral suspensionDrug: Fludrocortisone, tabletsDrug: Eplerenone, tablets

Interventions

AZD9977 oral suspensionDRUG

AZD9977 oral suspension, single dose

Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6Treatment Sequence 7Treatment Sequence 8
AZD9977 placebo oral suspensionDRUG

oral suspension, single dose

Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6Treatment Sequence 7Treatment Sequence 8
Fludrocortisone, tabletsDRUG

Loading dose of 0.5 mg and maintenance doses of 0.1 mg every second hour up to a total dose of 1.0 mg per treatment period (may be modified to up to 1.3 mg based on emerging data)

Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6Treatment Sequence 7Treatment Sequence 8
Eplerenone, tabletsDRUG

100 mg (2 x 50 mg tablets) single dose, may be modified based on emerging data (will not exceed 500 mg per treatment period)

Treatment Sequence 1Treatment Sequence 2Treatment Sequence 3Treatment Sequence 4Treatment Sequence 5Treatment Sequence 6Treatment Sequence 7Treatment Sequence 8

Eligibility Criteria

Age18 Years - 50 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (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 must accept 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.
  • Note: Participation in exploratory biomarker research is mandatory. 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 gastrointestinal, 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 first dosing with investigational medicinal product (IMP).
  • Any clinically significant abnormalities in hematology, clinical chemistry or urinalysis results, as judged by the investigator.
  • 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 \> 85 beats per minute (bpm)
  • Any clinically significant abnormalities on the 12-lead electrocardiogram (ECG), 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.
  • Known or suspected history of drug abuse, as judged by the investigator.
  • Note: Subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded.
  • Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening.
  • History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977.
  • Current smokers or those who have smoked or used nicotine products within the previous 3 months.
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Research Site

Harrow, United Kingdom

Location

MeSH Terms

Interventions

FludrocortisoneTabletsEplerenone

Intervention Hierarchy (Ancestors)

HydrocortisonePregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsDosage FormsPharmaceutical PreparationsLactonesOrganic Chemicals

Results Point of Contact

Title
AZD9977 Global Clinical Leader
Organization
AstraZeneca AB
ClinicalTrialTransparency@astrazeneca.com
+46317761000

Study Officials

  • Muna Albayaty, MBChB, MSc, MFPM

    PAREXEL Early Phase Clinical Unit London

    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
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 24, 2015

First Posted

August 26, 2015

Study Start

September 1, 2015

Primary Completion

December 1, 2015

Study Completion

December 1, 2015

Last Updated

March 29, 2017

Results First Posted

March 29, 2017

Record last verified: 2017-02

Locations

GB(1)