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.
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
14
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.
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.
Research Site
Baltimore, Maryland, United States
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
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
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
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
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
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
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
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
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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
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)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole.
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)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
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)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
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)
To access pharmacokinetics (PK) of AZD9977 in healthy volunteers when administered alone and in combination with multiple doses of itraconazole
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)
To assess AEs as variable of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
To assess the white blood cell count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
To assess the red blood cell count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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)
To assess the Hb as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
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.
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)
To assess the MCH as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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)
To assess the MCV as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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)
To assess the MCHC as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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
To assess the neutrophils absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
To assess the Lymphocytes absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
To assess the Monocytes absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
To assess the Eosinophils absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
To assess the Basophils absolute count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
To assess the Platelets count as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole
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
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.
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
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.
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
To assess the albumin level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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)
To assess the CRP level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazol
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)
To assess the CK level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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
To assess the creatinine level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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)
To assess the fasting glucose level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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
To assess the uric acid level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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
To assess the BUN level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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)
To assess the TBL level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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
To assess the indirect bilirubin as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
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)
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.
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)
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.
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
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 \[cellular, granular, hyaline\]).
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
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 \[cellular, granular, hyaline\]).
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
To assess the urine glucose level as variables of safety and tolerability after administration of single dose of AZD9977 in combination with itraconazole.
Time frame: From screening (Day -28) till follow-up visit (up to approximately 6 weeks)