Heart Failure With Preserved Ejection Fraction (HFpEF)Phase 1NCT03843060
A Phase 1 Study to Assess the Pharmacokinetics of AZD9977 Administered Alone and in Combination With Itraconazole in Healthy Volunteers
A Phase 1 study testing AZD9977 and Itraconazole in people with Heart Failure With Preserved Ejection Fraction (HFpEF), run by AstraZeneca at 1 site in United States.
Trial summary
This is an open-label, non-randomized, fixed sequence study conducted at a single study center with primary aim to assess the pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction (HFpEF)
- What is being tested?
- AZD9977 and Itraconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2019to 1 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- 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 and female participants of non-childbearing potential aged 18 - 55 years with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
- Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels ≥40 mlU/ml.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
- 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.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer'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 the first administration of IMP.
- Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI including serum potassium > 5.0 mmol/L, serum hsTnI > 25.6 pg/mL, and NT-pro-BNP > 124 pg/mL.
- 5. Any clinically significant abnormal findings in vital signs as specified below and as judged by the PI at screening and on admission including:
- Systolic blood pressure (SBP) < 90 mmHg or > 140 mmHg.
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- Diastolic blood pressure (DBP) < 50 mmHg or > 90 mmHg.
- HR < 45 or > 90 beats per minute (bpm). 6. Any clinically significant abnormalities on 12-lead ECG, as judged by the PI.
- 7. Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- 8. Known or suspected history of drug abuse in the last 12 months as judged by the Investigator.
- 9. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
- 10. Plasma donation within 1 month of screening or any blood donation/loss more than 500 mL during the 3 months prior to screening.
- 11. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the PI or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977.
- 12. Current smokers or those who have smoked or used nicotine products (including e cigarettes) within the 3 months prior to screening.
- 13. Positive screen for drugs of abuse, cotinine or alcohol at screening or on each admission to the study center.
- 14. Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- 15. 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 the 2 weeks prior to the first administration of IMP or longer if the medication has a long half life.
- 16. Known or suspected history of alcohol or drug abuse or excessive intake of alcohol in the last 12 months as judged by the PI.
- 17. Involvement of any AstraZeneca, PAREXEL or study site employee or their close relatives.
- 18. Participants who have previously received AZD9977. 19. Judgment by the PI that the participant 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.
- 20. Vulnerable participants , e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- 21. Participants with any special dietary restrictions such as participants that are lactose intolerant or are vegetarians/vegans.
- 22. Drugs affecting CYP3A4 (itraconazole) should be refrained from use for 3 weeks prior to study commencement and thereafter until study completion.
- 23. The following exclusion criterion is driven by contraindications from the proposed concomitant CYP3A4 (itraconazole) inhibitor medications: Itraconazole (Sporanox) capsules are contra-indicated in patients with known hypersensitivity to itraconazole or to any of the excipients.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Single Center Open-label, Non-randomized, Fixed Sequence Study in Healthy Volunteers to Assess the Pharmacokinetics (PK) of AZD9977 When Administered Alone and With Itraconazole
This is an open-label, non-randomized, fixed sequence study conducted at a single study center with primary aim to assess the pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole.
Read the detailed description
This is an open-label, non-randomized, fixed sequence study conducted at a single study center with primary aim to assess the pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole. Two types of treatments (treatment period 1 and treatment period 2) will be administered in a fixed order separated by a washout period of 3 days or more. Treatment period 1 will be single dose of AZD9977 (Dose 1) administration, in the fed state, on Day 1 followed by at least 3 days washout period. For treatment period 2, Itraconazole will be administered daily (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) will be administered as a single dose on Day 7. Dose of itraconazole has to be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.
- Being tested
- AZD9977, Itraconazole
- Keywords
- Congestive heart failure, Healthy volunteers, Itraconazole, Drug-drug interaction, Pharmacokinetics, Open-label non-randomized
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9977Drug
Participants will receive single AZD9977 (Dose 1) capsule orally once daily in fed state, on Day 1 followed by at least 3 days washout period.
ItraconazoleDrug
Also called Sporanox
Participants will receive Itraconazole daily (Dose 2) capsule orally once daily from Day 4 to Day 8 plus will be administered AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole has to be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.
| Study group | Role | What they receive |
|---|---|---|
| Single AZD9977 | Experimental | During this treatment period, healthy participants will be administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period. Receives: Drug: AZD9977 |
| Itraconazole + AZD9977 | Experimental | During this treatment period, healthy participants will be administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus will be administrated with AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole will be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977. Receives: Drug: Itraconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under plasma concentration-time curve from time zero to infinity (AUC) for AZD9977
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) for AZD9977
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Maximum observed plasma concentration (Cmax) for AZD9977
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Secondary outcomes (40)
Time to reach Maximum Observed Plasma Concentration (tMax)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Mean residence time of the unchanged drug in the systemic circulation from time zero to infinity (MRT)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole.
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Terminal elimination rate constant (λz)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Apparent total body clearance of drug from plasmsa after extravascular administration (CL/F)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Measured: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Number of participants with adverse events (AEs)
To assess AEs as variable of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal blood pressure (both systolic and diastolic blood pressure)
To measure BP as variable of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole. BP will be collected after the participants has rested in the supine position for at least 5 minutes.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal pulse rate
To measure pulse rate as variable of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole. Pulse rate will be collected after the participants has rested in the supine position for at least 5 minutes.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal 12-lead Electrocardiograms (ECG)
To examine the safety and tolerability of AZD9977 in combination with itraconazole. 12-lead safety ECG will be obtained after the participant rested in the supine position for at least 10 minutes using the sites own ECG machines. The Principal Investigator (PI) will judge the overall interpretation as normal or abnormal and this evaluation will be reported in ClinBase. If abnormal, it will be further documented as to whether or not the abnormality is clinically significant by the PI.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal physical examination findings
To assess any clinically significant abnormal physical examination findings as a variable of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole. The complete physical examinations will include an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. The brief physical examinations will include an assessment of the general appearance, skin, abdomen, cardiovascular system and respiratory.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- White blood cell (WBC) count
To assess the white blood cell count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participnats with abnormal laboratory assessments: Hematology- Red blood cell (RBC) count
To assess the red blood cell count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of paticipants with abnormal laboratory assessments: Hematology - Hemoglobin (Hb)
To assess the Hb as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Hematocrit (HCT) and Reticulocyte absolute count
To assess the HCT and reticulocyte absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
To assess the MCH as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Mean corpuscular volume (MCV)
To assess the MCV as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
To assess the MCHC as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Neutrophils absolute count
To assess the neutrophils absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnotmal laboratory assessments: Hematology- Lymphocytes absolute count
To assess the Lymphocytes absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Monocytes absolute count
To assess the Monocytes absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Eosinophils absolute count
To assess the Eosinophils absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Basophils absolute count
To assess the Basophils absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Platelets count
To assess the Platelets count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Calcium, potassium, phosphate and sodium
To assess the serum calcium, potassium, phosphate and sodium level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Liver enzymes
To assess the serum Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Albumin
To assess the albumin level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - C reactive protein (CRP)
To assess the CRP level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazol
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Creatine kinase (CK)
To assess the CK level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Creatinine
To assess the creatinine level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Glucose (fasting)
To assess the fasting glucose level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry- Uric acid
To assess the uric acid level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry- BUN
To assess the BUN level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Total Bilirubin (TBL)
To assess the TBL level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Indirect bilirubin
To assess the indirect bilirubin as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - High-sensitivity troponin I ((hsTnI)
To assess the High-sensitivity troponin I ((hsTnI) as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - N-terminal-pro-brain natriuretic peptide (NT-pro-BNP)
To assess the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Clinical Urinalysis - Protein
To assess the urine protein level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole. If urinalysis is positive for protein, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]).
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Clinical Urinalysis - Blood
To assess the urine blood level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole. If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]).
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Clinical Urinalysis - Glucose
To assess the urine glucose level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Measured: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start22 Feb 2019
- Primary completion1 Apr 2019
- Study completion1 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection Fraction (HFpEF)Studies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ronald Goldwater, Principal investigator, Dr.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03843060
- Sponsor's protocol ID
- D6401C00003
- Status last verified
- Apr 2019
- First submitted
- 14 Feb 2019
- Last updated
- 22 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Single Center Open-label, Non-randomized, Fixed Sequence Study in Healthy Volunteers to Assess the Pharmacokinetics (PK) of AZD9977 When Administered Alone and With Itraconazole
- ClinicalTrials.gov ID
- NCT03843060
- Acronym / sponsor ID
- D6401C00003
- Keywords
- Congestive heart failure, Healthy volunteers, Itraconazole, Drug-drug interaction, Pharmacokinetics, Open-label non-randomized
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 22 Feb 2019 (actual)
- Primary completion
- 1 Apr 2019 (actual)
- Study completion
- 1 Apr 2019 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-randomized, fixed sequence study conducted at a single study center with primary aim to assess the pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole.
Detailed description
This is an open-label, non-randomized, fixed sequence study conducted at a single study center with primary aim to assess the pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole. Two types of treatments (treatment period 1 and treatment period 2) will be administered in a fixed order separated by a washout period of 3 days or more. Treatment period 1 will be single dose of AZD9977 (Dose 1) administration, in the fed state, on Day 1 followed by at least 3 days washout period. For treatment period 2, Itraconazole will be administered daily (Dose 2) from Day 4 to Day 8 plus AZD9977 (Dose 1, fed state) will be administered as a single dose on Day 7. Dose of itraconazole has to be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Single AZD9977 | Experimental | Drug: AZD9977During this treatment period, healthy participants will be administered with a single AZD9977 (Dose 1) dose, in the fed state, on Day 1 followed by at least 3 days washout period. |
| Itraconazole + AZD9977 | Experimental | Drug: ItraconazoleDuring this treatment period, healthy participants will be administered with Itraconazole (Dose 2) from Day 4 to Day 8 plus will be administrated with AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole will be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Provision of signed and dated, written informed consent prior to any study specific procedures.
- Healthy male and female participants of non-childbearing potential aged 18 - 55 years with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
- 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.
Key exclusion criteria (24 listed)
- History of any clinically significant disease or disorder which, in the opinion of the PI, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer'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 the first administration of IMP.
- Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the PI including serum potassium > 5.0 mmol/L, serum hsTnI > 25.6 pg/mL, and NT-pro-BNP > 124 pg/mL.
- 5. Any clinically significant abnormal findings in vital signs as specified below and as judged by the PI at screening and on admission including:
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 |
|---|---|---|
| AZD9977Participants will receive single AZD9977 (Dose 1) capsule orally once daily in fed state, on Day 1 followed by at least 3 days washout period. | Drug | Single AZD9977 |
| ItraconazoleAlso: SporanoxParticipants will receive Itraconazole daily (Dose 2) capsule orally once daily from Day 4 to Day 8 plus will be administered AZD9977 (Dose 1, fed state) as a single dose on Day 7. Dose of itraconazole has to be taken at -1 hour (1 hour prior to AZD9977 dosing) when co-administered with AZD9977. | Drug | Itraconazole + AZD9977 |
Primary outcome
Area under plasma concentration-time curve from time zero to infinity (AUC) for AZD9977
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) for AZD9977
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
Maximum observed plasma concentration (Cmax) for AZD9977
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
40 secondary outcomes
Time to reach Maximum Observed Plasma Concentration (tMax)
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Mean residence time of the unchanged drug in the systemic circulation from time zero to infinity (MRT)
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Terminal elimination rate constant (λz)
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Apparent total body clearance of drug from plasmsa after extravascular administration (CL/F)
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)
Time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose
Number of participants with adverse events (AEs)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal blood pressure (both systolic and diastolic blood pressure)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal pulse rate
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal 12-lead Electrocardiograms (ECG)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal physical examination findings
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- White blood cell (WBC) count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participnats with abnormal laboratory assessments: Hematology- Red blood cell (RBC) count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of paticipants with abnormal laboratory assessments: Hematology - Hemoglobin (Hb)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Hematocrit (HCT) and Reticulocyte absolute count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Mean corpuscular volume (MCV)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Neutrophils absolute count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnotmal laboratory assessments: Hematology- Lymphocytes absolute count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Monocytes absolute count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Eosinophils absolute count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Basophils absolute count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Hematology- Platelets count
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Calcium, potassium, phosphate and sodium
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Liver enzymes
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Albumin
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - C reactive protein (CRP)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Creatine kinase (CK)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Creatinine
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Glucose (fasting)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry- Uric acid
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry- BUN
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Total Bilirubin (TBL)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - Indirect bilirubin
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - High-sensitivity troponin I ((hsTnI)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Serum Clinical chemistry - N-terminal-pro-brain natriuretic peptide (NT-pro-BNP)
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Clinical Urinalysis - Protein
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Clinical Urinalysis - Blood
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Number of participants with abnormal laboratory assessments: Clinical Urinalysis - Glucose
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2019.
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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.
Ronald Goldwater principal investigator
Dr.
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 and Itraconazole in people with Heart Failure With Preserved Ejection Fraction (HFpEF), run by AstraZeneca at 1 site in United States.
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 6 inclusion and 24 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 22 Apr 2019. 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 States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Area under plasma concentration-time curve from time zero to infinity (AUC) for AZD9977 (time frame: Day 1 to 3: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose. Day 4 to 9: pre-dose on Day 7 and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36 and 48 hours post-dose). The study lists 3 primary outcomes in all. 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 22 Apr 2019.