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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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This study will evaluate pharmacokinetics (PK) of four different formulations with different release profiles of AZD9977 (PART A) in the fasted state, and one of the formulation will be selected for further development (Part B). In Part B, the influence of food on the PK of AZD9977 will be evaluated
This study is a randomized, open-label, single-center study conducted on 12 healthy male subjects. This consists of three periods:
The study is divided into 2 parts: Part A and B. The subjects will participate in both Part A and Part B. Part A will be a 4-way cross-over study to compare the PK of 3 different solid formulations with different release rates with an oral suspension of AZD9977 in fasting conditions. Subjects in Part A will receive the following treatments on Days 1, 3, 5 and 7:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment sequence 1 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 oral suspension (reference) AZD9977 capsule AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) |
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| Treatment sequence 2 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 capsule AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) AZD9977 oral suspension (reference) |
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| Treatment sequence 3 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 ER capsule (fast rate) AZD9977 ER capsule (Int. rate) AZD9977 Oral suspension (reference) AZD9977 capsule |
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| Treatment sequence 4 | Experimental | In Part A, randomized subjects will receive orally single dose of all treatments in fasted condition in the following sequence: AZD9977 ER capsule (Int. rate) AZD9977 Oral suspension (reference) AZD9977 capsule AZD9977 ER capsule (fast rate) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD9977 Oral suspension (reference) | Drug | Randomized subjects will receive single oral dose of AZD9977 oral suspension 15 mg/mL on Days 1, 3, 5 and 7 in Part A. |
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| Measure | Description | Time Frame |
|---|---|---|
| Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under plasma concentration-time curve from time zero to infinity (AUC) | To assess Frel by assessments of PK parameters AUC after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast) | To assess Frel by assessments of PK parameters AUClast after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Area under the plasma concentration-time curve from time zero to time 24 hours (AUC[0-24]) | To assess Frel by assessments of PK parameters AUC[0-24] after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Relative bioavailability (Frel) of AZD9977 capsule, ER (fast rate) and ER (Int. rate) capsules versus AZD9977 oral suspension (reference): Maximum observed plasma concentration (Cmax ) | To assess Frel by assessments of PK parameters Cmax after administration of single oral dose of AZD9977 capsule and ER (fast rate and Int. rate) capsules by comparison with AZD9977 oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma PK parameter: Plasma concentration 24 hours post-dose (C4) | To assess C24 after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A and Part B - Day 1 (24 hours post-dose) |
| Plasma PK parameter: Time to reach maximum observed plasma concentration (tmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | London | HA1 3UJ | United Kingdom |
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| AZD9977 capsule | Drug | Randomized subjects will receive single oral dose of AZD9977 capsule 65 mg on Days 1, 3, 5 and 7 in Part A. |
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| AZD9977 ER capsule (fastvrate) | Drug | Randomized subjects will receive single oral dose of AZD9977 ER capsule (fast rate) 65 mg on Days 1, 3, 5 and 7 in Part A. |
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| AZD9977 ER capsule (Int. rate) | Drug | Randomized subjects will receive single oral dose of AZD9977 ER capsule (Int rate) 65 mg on Days 1, 3, 5 and 7 in Part A. |
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| Plasma PK parameter: Area under plasma concentration-time curve from time zero to infinity (AUC) | To assess AUC after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) | To assess AUClast after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Maximum observed plasma concentration (Cmax) | To assess Cmax after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Area under the plasma concentration-time curve from time zero to time 24 hours (AUC[0-24]) | To assess AUC(0-24) after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7 |
| The Effect of food on the PK of one of the solid formultaion evaluated in Part A under fasting and fed conditions in Part B | To evaluate the influence of food by comparing AUC and Cmax under fasting and fed conditions for one of the solid formulations evaluated in Part A. | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
To assess tmax after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). |
| Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz ) | To assess t½λz after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) | To assess MRT after administration of single oral dose of AZD9977 capsule, ER (fast rate and Int. rate) capsules and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Terminal elimination rate constant (λz) | To assess λz after administration of single oral dose of AZD9977 capsule, ER (fast rate and Int. rate) capsules and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Apparent total body clearance of drug from plasma after extravascular administration AZD9977 (CL/F) | To assess CL/F after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Plasma PK parameter: Apparent volume of distribution during the terminal phase after extravascular administration AZD9977 (Vz/F) | To assess Vz/F after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | Dosing sessions: Part A: Days 1, 3, 5 and 7; Part B: Day 1 |
| Number of subjects with adverse events (AEs) due to AZD9977 | To assess AEs as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). AEs will be collected from the start of screening throughout the treatment period up to and including the follow-up visit. Serious AEs will be recorded from the time of informed consent. | From screening up to follow-up (5 to 7 days after final dose) |
| Vital sign: Blood pressure [BP] | To assess supine position systolic and diastolic BP as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). Both SBP and DBP will be collected after the subject has rested in the supine position for at least 5 minutes. | From screening up to follow-up (5 to 7 days after final dose) |
| Vital sign: Pulse rate | To assess supine position pulse rate as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). Pulse rate will be collected after the subject has rested in the supine position for at least 5 minutes. | From screening up to follow-up (5 to 7 days after final dose) |
| Number of participants with abnormal findings in Resting 12-lead Electrocardiogram (ECG) | To assess any clinically significant abnormalities in the cardiovascular system functioning using a 10-second 12-lead ECG as variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). The specific type and nature of the abnormality will be documented in ClinBase. Clinically significant findings will also be documented on the AE page of the CRF if applicable. | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| 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 oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). Brief physical examination includes assessment of the general appearance, skin, abdomen, cardiovascular system and respiratory. Full physical examination includes 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. | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Blood cells count | To assess red blood cells ( RBC) and white blood cells (WBC) countas a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Hemoglobin (Hb) | To assess Hb as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Hematocrit (HCT) and Reticulocyte absolute count | To assess HCT (RBC) and reticulocyte absolute count (immature RBCs) as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Mean corpuscular volume (MCV) | To assess MCV as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Mean corpuscular hemoglobin (MCH) | To assess MCH as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Mean corpuscular hemoglobin concentration (MCHC) | To assess MCHC as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Differential count | To assess differential WBC count (absolute count of neutrophils, lymphocytes, monocyets, eosinophils and basophils) as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Hematology - Platelets | To assess platelets count as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - sodium, potassium, calcium and phosphate | To assess serum sodium, potassium, calcium and phosphate level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - Urea and Uric acid | To assess serum urea and uric acid level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - Creatinine | To assess serum creatinine level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - Albumin | To assess serum albumin level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - Glucose (fasting) | To assess serum fasting glucose level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - C-reactive protein (CRP) | To assess serum CRP level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - Liver enzymes | To assess serum Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma glutamyl transpeptidase (GGT) level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - Bilirubin | To assess serum bilirubin (total and unconjugated) level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - High-sensitivity troponin T | To assess serum high-sensitivity troponin T level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - Creatine kinase | To assess serum creatine kinase level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Serum Clinical chemistry - N-terminal-pro-brain natriuretic peptide (NT-proBNP) | To assess serum NT-proBNP level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Clinical Urinalysis - Glucose | To assess urine glucose level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Clinical Urinalysis - Protein | To assess urine protein level as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). If urinalysis is positive for protein, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| Laboratory assessments: Clinical Urinalysis - Blood | To assess presence of blood in urine as a variable of safety and tolerability after administration of single oral dose of AZD9977 capsule, ER capsules (fast rate and Int. rate) and oral suspension (reference). If urinalysis is positive for blood, a microscopy test will be performed to assess RBC, WBC, casts [cellular, granular, hyaline]). | At screening, dosing sessions of Part A and Part B and follow-up (5 to 7 days after final dose) |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C000627339 | AZD9977 |
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