PharmacodynamicsPhase 1NCT02532998
A Study to Assess the Pharmacodynamic Effect of Single Doses of AZD9977 in Healthy Male Subjects
A Phase 1 study testing AZD9977 oral suspension, Fludrocortisone, tablets and Eplerenone, tablets in people with Pharmacodynamics and Healthy Subjects, run by AstraZeneca at 1 site in United Kingdom.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pharmacodynamics, Healthy Subjects
- What is being tested?
- AZD9977 oral suspension, Fludrocortisone, tablets and Eplerenone, tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2015to Dec 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 37Show fewer
- 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.
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of first dosing. The period of exclusion begins 3 months after the final dose or one month after the last visit whichever is the longest.
- 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.
- Positive screen for drugs of abuse, alcohol or cotinine at screening or for each admission to the study center.
- Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to first dosing.
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during 2 weeks prior to first dosing, or longer if the medication has a long half-life.
- Known or suspected history of alcohol or drug abuse or excessive intake of alcohol, as judged by the investigator.
- Involvement of any AstraZeneca or study site employee or their close relatives.
- Subjects who previously received AZD9977.
- Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements.
- Known allergy to eplerenone or fludrocortisone or any of the constituents (including lactose, which is a constituent of Florinef™).
- History of galactose intolerance.
- Any infections or at risk of infection (surgery, trauma, or significant infection) within 90 days of screening, or history of skin abscesses within 90 days of screening.
- Presence, history or family history of long QT syndrome, hypokalemia, hyperkalemia or Torsades de Pointes.
- Serum potassium < 3.5 mmol/L or ≥ 5.0 mmol/L at screening or for each admission to the study center.
- Presence or history of active peptic ulcer.
- History of any psychiatric disorder (including affective, psychotic, behavioral, irritability, anxiety, sleep disturbances and cognitive disorders) which required specialist psychiatric review.
- Excessive intake of caffeine containing drinks or food (e.g., coffee, tea and chocolate) as judged by the investigator.
- Subjects who are vegans or have medical dietary restrictions (vegetarians may be included in the study).
- Subjects who cannot communicate reliably with the investigator.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
- Previous bone marrow transplant.
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomized, Single-Blind, Crossover Study to Assess the Pharmacodynamics of AZD9977 Following Single-Dose Administration to Healthy Male Subjects
This is a Phase I, Randomized, Single-Blind, Crossover Study to Assess the Pharmacodynamics of AZD9977 following Single-Dose administration to healthy male subjects
Read the detailed description
This study will be a phase I study to assess the pharmacodynamics of AZD9977 following single-dose administration to healthy male subjects. It is a single-blind (with regards to AZD9977 and AZD9977 Placebo), randomized, four-treatment, four-period crossover design, with a potential 5th and 6th randomized cross-over treatment period. In this study eplerenone is used as a positive control and fludrocortisone will be used as a challenge agent. In addition the safety, tolerability and pharmacokinetics will be assessed.
- Conditions
- Pharmacodynamics, Healthy Subjects
- Being tested
- AZD9977 oral suspension, AZD9977 placebo oral suspension, Fludrocortisone, tablets, Eplerenone, tablets
- Keywords
- Pharmacodynamics, AZD9977, Safety, Tolerability, Pharmacokinetics, Eplerenone, Fludrocortisone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9977 oral suspensionDrug
AZD9977 oral suspension, single dose
AZD9977 placebo oral suspensionDrug
oral suspension, single dose
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)
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)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: 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 Receives: Drug: AZD9977 oral suspension; Drug: AZD9977 placebo oral suspension; Drug: Fludrocortisone, tablets; Drug: Eplerenone, tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From 2 hours post dose to 8 hours post dose
Secondary outcomes (26)
Observed Maximum Concentration (Cmax) of AZD9977
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: 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.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Time to Reach Maximum Concentration (Tmax) of AZD9977.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Terminal Half-life (t½λz) of AZD9977.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Apparent Clearance (CL/F) of AZD9977.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Apparent Clearance (CL/F) of Eplerenone.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Terminal Half-life (t½λz) of Eplerenone.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Time to Reach Maximum Concentration (Tmax) of Eplerenone.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Observed Maximum Concentration (Cmax) of Eplerenone.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: 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 Eplerenone.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone.
Pre IMP dose and post IMP dose at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours
Measured: From 2 hours post dose to 8 hours post dose
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With 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: 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.
Measured: From 2 hours post dose to 8 hours post dose
Number of Participants With Clinically Significant Blood Pressure Values.
Clinically significant blood pressure values (if available) were recorded for all participants.
The systolic blood pressure (mmHg) and diastolic BP (mmHg) was obtained after each subject had rested in the supine position for at least 5 minutes and was performed in accordance with the Schedule of Assessments of study protocol.
Abnormal findings in blood pressure after 10 minutes resting in the supine position was defined as following:
- Systolic blood pressure (SBP) < 90 mmHg or ≥ 140 mmHg
- Diastolic blood pressure (DBP) < 50 mmHg or ≥ 90 mmHg.
Measured: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Pulse Rate.
Clinically significant pulse rate (if available) was recorded for all participants in the study.
The pulse was obtained after each subject had rested in the supine position for at least 5 minutes and was performed in accordance with the Schedule of Assessments of study protocol.
Abnormal findings in pulse rate, after 10 minutes resting in the supine position, was defined as following:
- Pulse < 45 or > 85 beats per minute (bpm)
Measured: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Electrocardiogram.
Clinically significant electrocardiogram values were recorded for all participants in the study.
A 12-lead ECG was obtained after each subject had rested in the supine position for at least 10 minutes and was performed in accordance with the Schedule of Assessments of study protocol.
The investigator judged the overall interpretation as normal or abnormal. If abnormal, it would have been decided as to whether or not the abnormality was clinically significant and the reason for the abnormality would have been recorded. The investigator could add extra 12-lead resting ECG safety assessments if there were any abnormal findings of if the investigator considered it was necessary for any other safety reason. These assessments would have been entered as an unscheduled assessment.
Measured: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Physical Examination Values.
Number of participants with clinically significant physical examination values.
The complete physical examinations included an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, mouth and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. The brief physical examinations included an assessment of the general appearance, skin, abdomen, cardiovascular and respiratory systems. The results of the physical examination were listed by body system for each subject. Body weight was listed by participant and time-point. Any new or aggravated clinically relevant abnormal medical finding at a physical examination as compared with the baseline assessment were reported as an adverse event (AE).
Measured: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Safety Laboratory Tests Values.
Clinically significant safety laboratory test values included hematology, clinical chemistry, urinalysis and urine chemistry, including urine creatinine and uric acid measurements. Viral serology and urine drugs of abuse, alcohol and cotinine were assessed for eligibility. If deterioration in laboratory value was associated with clinical symptoms and/or signs, the symptom or sign were reported as an adverse event and the associated laboratory result was considered as additional information. Laboratory results were listed and summarized according to change from baseline and repeat/unscheduled measurements. Any out of range laboratory results were flagged in the individual listings.
Measured: From screening to post-study visit, up to 10 weeks
Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
Pharmacodynamics of AZD9977 by assessment of fractional sodium excretion in urine for each urine collection time interval.
Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone.
Measured: From 0 to 8 hours after dosing
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
Pharmacodynamics of AZD9977 by assessment of total sodium excreted cumulatively and during each of the urine collection intervals.
Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone.
Measured: From 0 to 24 hours after dosing
Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
Pharmacodynamics of AZD9977 assessed per fractional potassium excretion in urine for each urine collection time interval.
Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone
Measured: From 0 to 8 hours post dosing
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
Pharmacodynamics of AZD9977 by assessment of total potassium excreted cumulatively and during each of the urine collection intervals.
Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone in comparison to AZD9977 placebo.
Measured: From 0 to 24 hours after dosing
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
Pharmacodynamics of AZD9977 assessed per urine production for each urine collection time interval.
Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone.
Measured: From 8 hours before dosing until 24 hours after dosing
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
Pharmacodynamics of AZD9977 by assessment of total urine volume excreted cumulatively and during each of the urine collection intervals.
Pharmacodynamics of AZD9977 after single dosing of AZD9977 with fludrocortisone and/or eplerenone
Measured: From 8 hours before dosing until 24 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2015 (estimated)
- Study startSep 2015
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PharmacodynamicsStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Muna Albayaty, MBChB, MSc, MFPM, Principal investigator, PAREXEL Early Phase Clinical Unit London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02532998
- Sponsor's protocol ID
- D6400C00004
- Other IDs
- 2015-002224-11, 2015
- Status last verified
- Feb 2017
- First submitted
- 24 Aug 2015
- Last updated
- 29 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Single-Blind, Crossover Study to Assess the Pharmacodynamics of AZD9977 Following Single-Dose Administration to Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02532998
- Acronym / sponsor ID
- D6400C00004
- Conditions
- Pharmacodynamics, Healthy Subjects
- Keywords
- Pharmacodynamics, AZD9977, Safety, Tolerability, Pharmacokinetics, Eplerenone, Fludrocortisone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- Sep 2015
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 26 Aug 2015 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I, Randomized, Single-Blind, Crossover Study to Assess the Pharmacodynamics of AZD9977 following Single-Dose administration to healthy male subjects
Detailed description
This study will be a phase I study to assess the pharmacodynamics of AZD9977 following single-dose administration to healthy male subjects. It is a single-blind (with regards to AZD9977 and AZD9977 Placebo), randomized, four-treatment, four-period crossover design, with a potential 5th and 6th randomized cross-over treatment period. In this study eplerenone is used as a positive control and fludrocortisone will be used as a challenge agent. In addition the safety, tolerability and pharmacokinetics will be assessed.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence 1 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
| Treatment Sequence 2 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
| Treatment Sequence 3 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
| Treatment Sequence 4 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
| Treatment Sequence 5 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
| Treatment Sequence 6 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
| Treatment Sequence 7 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
| Treatment Sequence 8 | Experimental | Drug: AZD9977 oral suspension, Drug: AZD9977 placebo oral suspension, Drug: Fludrocortisone, tablets, Drug: Eplerenone, tabletsPeriod 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 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (37 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD9977 oral suspensionAZD9977 oral suspension, single dose | Drug | Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6, Treatment Sequence 7, Treatment Sequence 8 |
| AZD9977 placebo oral suspensionoral suspension, single dose | Drug | Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6, Treatment Sequence 7, Treatment Sequence 8 |
| Fludrocortisone, tabletsLoading 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) | Drug | Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6, Treatment Sequence 7, Treatment Sequence 8 |
| Eplerenone, tablets100 mg (2 x 50 mg tablets) single dose, may be modified based on emerging data (will not exceed 500 mg per treatment period) | Drug | Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6, Treatment Sequence 7, Treatment Sequence 8 |
Primary outcome
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977.
Time frame: From 2 hours post dose to 8 hours post dose
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.
26 secondary outcomes
Observed Maximum Concentration (Cmax) of AZD9977
Time frame: From 2 hours post dose to 8 hours post dose
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of AZD9977.
Time frame: 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.
Time frame: From 2 hours post dose to 8 hours post dose
Time to Reach Maximum Concentration (Tmax) of AZD9977.
Time frame: From 2 hours post dose to 8 hours post dose
Terminal Half-life (t½λz) of AZD9977.
Time frame: From 2 hours post dose to 8 hours post dose
Apparent Clearance (CL/F) of AZD9977.
Time frame: From 2 hours post dose to 8 hours post dose
Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD9977.
Time frame: From 2 hours post dose to 8 hours post dose
Apparent Volume of Distribution at Terminal Phase (Vz/F) of Eplerenone.
Time frame: From 2 hours post dose to 8 hours post dose
Apparent Clearance (CL/F) of Eplerenone.
Time frame: From 2 hours post dose to 8 hours post dose
Terminal Half-life (t½λz) of Eplerenone.
Time frame: From 2 hours post dose to 8 hours post dose
Time to Reach Maximum Concentration (Tmax) of Eplerenone.
Time frame: From 2 hours post dose to 8 hours post dose
Observed Maximum Concentration (Cmax) of Eplerenone.
Time frame: 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 Eplerenone.
Time frame: From 2 hours post dose to 8 hours post dose
Area Under Plasma Concentration-time Curve From Zero Extrapolated to Infinity (AUC) of Eplerenone.
Time frame: From 2 hours post dose to 8 hours post dose
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in AZD9977 Treatment With Placebo Versus Treatment With AZD9977.
Time frame: From 2 hours post dose to 8 hours post dose
Number of Participants With Clinically Significant Blood Pressure Values.
Time frame: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Pulse Rate.
Time frame: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Electrocardiogram.
Time frame: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Physical Examination Values.
Time frame: From screening to post-study visit, up to 10 weeks
Number of Participants With Clinically Significant Safety Laboratory Tests Values.
Time frame: From screening to post-study visit, up to 10 weeks
Pharmacodynamics of AZD9977 Assessed by Estimating the Fractional Sodium Excretion in Urine for Each Urine Collection Time Interval.
Time frame: From 0 to 8 hours after dosing
Pharmacodynamics of AZD9977 Assessed Per Total Sodium Excreted Cumulatively and During Each of the Urine Collection Intervals.
Time frame: From 0 to 24 hours after dosing
Pharmacodynamics of AZD9977 Assessed Per Fractional Potassium Excretion in Urine for Each Urine Collection Time Interval.
Time frame: From 0 to 8 hours post dosing
Pharmacodynamics of AZD9977 by Assessment of Total Potassium Excreted Cumulatively and During Each of the Urine Collection Intervals
Time frame: From 0 to 24 hours after dosing
Pharmacodynamics of AZD9977 Assessed Per Urine Production for Each Urine Collection Time Interval.
Time frame: From 8 hours before dosing until 24 hours after dosing
Pharmacodynamics of AZD9977 by Assessment of Total Urine Volume Excreted Cumulatively and During Each of the Urine Collection Intervals
Time frame: From 8 hours before dosing until 24 hours after dosing
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Muna Albayaty, MBChB, MSc, MFPM principal investigator
PAREXEL Early Phase Clinical Unit London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD9977 oral suspension, Fludrocortisone, tablets and Eplerenone, tablets in people with Pharmacodynamics and Healthy Subjects, run by AstraZeneca at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacodynamics of AZD9977 Assessed Per Sodium/Potassium Ratio in Urine in Eplerenone Treatment Versus a Combination Treatment of Eplerenone and AZD9977. (time frame: From 2 hours post dose to 8 hours post dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2017; AzTrials last refreshed its copy on 6 Nov 2026.