Healthy Subjects, Pharmacokinetics, Safety, Tolerability
Conditions
Keywords
AZD9977, Safety, Tolerability, Pharmacokinetics, First-in-human, Single Ascending Dose, Regional absorption, Healthy male subjects
Brief summary
This study will be a randomized, single-blind, placebo-controlled first-in-human study in healthy male subjects to assess the safety, tolerability and pharmacokinetics of single ascending doses of AZD9977. In Part B of this study the regional absorption of AZD9977 along the gastro-intestinal tract will be investigated using the IntelliCap® system in a non-randomized, open-label, fixed-sequence design. The study will be performed at a single study centre.
Detailed description
This study will be a randomized, single-blind, placebo-controlled first-in-human study in healthy male subjects to assess the safety, tolerability and pharmacokinetics of single ascending doses of AZD9977. In Part B of this study the regional absorption of AZD9977 along the gastro-intestinal tract will be investigated using the IntelliCap® system in a non-randomized, open-label, fixed-sequence design with oral solution as reference. The study will be performed at a single study centre.
Interventions
DRUGAZD9977, oral suspension
Single ascending doses of AZD9977 oral suspension (Part A) Single dose of AZD9977 oral suspension in IntelliCap® capsule in regional absorption part (Part B)
DRUGPlacebo, oral suspension
Matching placebo
DRUGAZD9977, oral solution
AZD9977, single dose of oral solution in Part B as reference
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated written informed consent prior to any study specific procedures. 2. Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture. 3. Male subjects have to comply with the restrictions for sexual activity provided to them. 4. 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. 5. Optional: Provision of signed and dated written informed consent for genetic research. 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. 6. Able to understand, read and speak the English language.
Exclusion criteria
1. 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. 2. History or presence of GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs. 3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of dosing in Part A or the first dose of AZD9977 in Part B. 4. Any clinically significant abnormalities in hematology, clinical chemistry or urinalysis results, as judged by the investigator. 5. Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibodies. 6. Abnormal findings in vital signs, after 10 minutes resting in the supine position, defined as any of the following: * Systolic blood pressure (SBP) \< 90 mmHg or ≥ 140 mmHg * Diastolic blood pressure (DBP) \< 50 mmHg or ≥ 90 mmHg * Pulse \< 45 or \> 90 bpm 7. Any clinically important abnormalities in rhythm, conduction or morphology of the electrocardiogram (ECG) at screening or pre-dose, as considered by the investigator. 8. Prolonged QTcF \> 450 ms or family history of long QT syndrome. 9. PR (PQ) interval shortening \< 120 ms. PR \> 110 ms but \< 120 ms is acceptable if there is no evidence of ventricular pre-excitation. 10. PR (PQ) interval prolongation \> 240ms; intermittent second or third degree atrioventricular (AV) block, or AV dissociation. Wenckebach block while asleep is not exclusive. 11. Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS \> 110 ms. QRS \> 110 ms but \< 115 ms are acceptable if there is no evidence of ventricular hypertrophy or pre-excitation. 12. Serum potassium higher than 5.0 mmol/L at screening or admission to the study center (Day -1). 13. Known or suspected history of drug abuse as judged by the investigator. 14. Current smokers or those who have smoked or used nicotine products within the previous 3 months. 15. History of alcohol abuse or excessive intake of alcohol as judged by the investigator. 16. Positive screen for drugs of abuse, alcohol or cotinine at screening or admission to the study center. 17. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9977. 18. Excessive intake of caffeine containing drinks or food (e.g., coffee, tea and chocolate) as judged by the investigator. 19. Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to dosing in Part A or the first dose of AZD9977 in Part B. 20. 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 dosing in Part A or the first dose of AZD9977 in Part B, or longer if the medication has a long half-life. 21. Plasma donation within one month of screening or any blood donation/blood loss \> 500 mL during the 3 months prior to screening. 22. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of dosing in Part A or the first dose of AZD9977 in Part B in this study. 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. 23. Involvement of any AstraZeneca or study site employee or their close relatives. 24. 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. 25. Subjects who are vegans or have medical dietary restrictions (vegetarians may be included in the study). 26. Subjects who cannot communicate reliably with the investigator. 27. 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: 28. Previous bone marrow transplant. 29. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection. Criteria applicable to Part B only: 30. Subjects with pacemakers or other implanted electro-medical devices. 31. Subjects with swallowing disorders. 32. Subjects with pre-planned MRI examination. 33. Subjects not willing to have an abdominal X-ray performed if the IntelliCap® capsule has not been retrieved within one week after ingestion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | For up to 4 days, i.e. on the day before each dosing and for 24 hours after each dosing | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
| Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | For up to 45 days, i.e. from Screening to Follow-up | To assess the safety and tolerability of single ascending doses of AZD9977 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | Pre-dose and post-dose upto 48 hrs | To assess urine pharmacokinetic parameters following single ascending doses of AZD9977 |
| Renal Clearance of Drug From Plasma [CLR (0-48)] | Pre-dose and post-dose upto 48 hrs | To assess urine pharmacokinetic parameters following single ascending doses of AZD9977 |
| Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | Pre-dose and post-dose upto 48 hrs | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | Pre-dose and post-dose upto 48 hrs | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Observed Maximum Concentration (Cmax) | Pre-dose and post-dose upto 48 hrs | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time to Maximum Observed Plasma Concentration (t Max) | Pre-dose and post-dose upto 48 hrs | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | Pre-dose and post-dose upto 48 hrs | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Apparent Clearance (CL/F) | Pre-dose and post-dose upto 48 hrs | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Apparent Volume of Distribution (Vz/F) | Pre-dose and post-dose upto 48 hrs | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Fraction Excreted Unchanged in Urine[Fe (0-48)] | Pre-dose and post-dose upto 48 hrs | To assess percentage of the total drug excreted in the urine that was unchanged following single ascending doses of AZD9977 |
Countries
United Kingdom
Participant flow
Recruitment details
This study was conducted at PAREXEL International, Early Phase Clinical Unit London, United Kingdom.
Pre-assignment details
In this study, 196 subjects were screened out of which 70 subjects were randomized. The study was conducted in two parts (Parts A and B). Part A-eight cohorts of 8 subjects, randomized in 6:2 (AZD9977: placebo) and Part B -1 cohort of 8 subjects who received a single dose of AZD9977, on 2 occasions separated by washout period of 7 days.
Participants by arm
| Arm | Count |
|---|---|
| Part A- Placebo Subjects received matching placebo under fasted conditions | 16 |
| Part A - 5 mg AZD9977 Subjects received 5 mg AZD9977, oral suspension under fasted conditions | 6 |
| Part A - 25 mg AZD9977 Subjects received 25 mg AZD9977, oral suspension under fasted conditions | 6 |
| Part A - 100 mg AZD9977 Subjects received 100 mg AZD9977, oral suspension under fasted conditions | 6 |
| Part A - 200 mg AZD9977 Subjects received 200 mg AZD9977, oral suspension under fasted conditions | 5 |
| Part A - 400 mg AZD9977 Subjects received 400 mg AZD9977, oral suspension under fasted conditions | 6 |
| Part A - 800 mg AZD9977 Subjects received 800 mg AZD9977, oral suspension under fasted conditions | 5 |
| Part A - 800 mg AZD9977 (Split Doses) Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | 6 |
| Part A - 1200 mg AZD9977 (Split Doses) Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 6 |
| Part B Subjects received a single dose of AZD9977, under fasted conditions, on two occasions (40 mg AZD9977, IntelliCap device and 40 mg AZD9977, oral solution) separated by a washout period of at least 7 days | 8 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Failure of IntelliCap Error | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A- Placebo | Part A - 5 mg AZD9977 | Part A - 25 mg AZD9977 | Part A - 100 mg AZD9977 | Part A - 200 mg AZD9977 | Part A - 400 mg AZD9977 | Part A - 800 mg AZD9977 | Part A - 800 mg AZD9977 (Split Doses) | Part A - 1200 mg AZD9977 (Split Doses) | Part B | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 30 Years STANDARD_DEVIATION 6 | 32 Years STANDARD_DEVIATION 11 | 30 Years STANDARD_DEVIATION 9 | 36 Years STANDARD_DEVIATION 10 | 32 Years STANDARD_DEVIATION 10 | 33 Years STANDARD_DEVIATION 9 | 30 Years STANDARD_DEVIATION 6 | 32 Years STANDARD_DEVIATION 8 | 38 Years STANDARD_DEVIATION 11 | 35 Years STANDARD_DEVIATION 9 | 33 Years STANDARD_DEVIATION 9 |
| Sex/Gender, Customized Male | 16 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 8 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 16 | 1 / 6 | 2 / 6 | 2 / 6 | 1 / 5 | 1 / 6 | 0 / 5 | 2 / 6 | 1 / 6 | 3 / 8 |
| serious Total, serious adverse events | 0 / 16 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure | 0 Number of Participants |
Primary
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry | 0 Number of participants |
Primary
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology | 0 Number of participants |
Primary
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis | 0 Number of participants |
Primary
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate | 0 Number of Participants |
Primary
Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms | 0 Number of participants |
Primary
Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 7 Number of Participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 1 Number of Participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 2 Number of Participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 2 Number of Participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 1 Number of Participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 2 Number of Participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 0 Number of Participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 2 Number of Participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 1 Number of Participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events | 3 Number of Participants |
Primary
Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 45 days, i.e. from Screening to Follow-up
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 43.8 percentage of participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 16.7 percentage of participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 33.3 percentage of participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 33.3 percentage of participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 20.0 percentage of participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 33.3 percentage of participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 0 percentage of participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 33.3 percentage of participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 16.7 percentage of participants |
| Part B | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events | 37.5 percentage of participants |
Primary
Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry
To assess the safety and tolerability of single ascending doses of AZD9977
Time frame: For up to 4 days, i.e. on the day before each dosing and for 24 hours after each dosing
Population: All subjects who received at least one dose of IMP and for whom any safety post-dose data were available were included in the safety analysis for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A- Placebo | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 5 mg AZD9977 | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 25 mg AZD9977 | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 100 mg AZD9977 | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 200 mg AZD9977 | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 400 mg AZD9977 | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 800 mg AZD9977 | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 800 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part A - 1200 mg AZD9977 (Split Doses) | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
| Part B | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry | 0 Number of Participants |
Secondary
Apparent Clearance (CL/F)
To assess plasma pharmacokinetic parameters following single ascending doses of AZD977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Apparent Clearance (CL/F) | 24.52 L/h | Standard Deviation 3.391 |
| Part A - 5 mg AZD9977 | Apparent Clearance (CL/F) | 25.89 L/h | Standard Deviation 5.546 |
| Part A - 25 mg AZD9977 | Apparent Clearance (CL/F) | 28.46 L/h | Standard Deviation 11.08 |
| Part A - 100 mg AZD9977 | Apparent Clearance (CL/F) | 21.84 L/h | Standard Deviation 5.812 |
| Part A - 200 mg AZD9977 | Apparent Clearance (CL/F) | 28.49 L/h | Standard Deviation 7.392 |
| Part A - 400 mg AZD9977 | Apparent Clearance (CL/F) | 54.34 L/h | Standard Deviation 19.16 |
| Part A - 800 mg AZD9977 | Apparent Clearance (CL/F) | 20.99 L/h | Standard Deviation 6.683 |
| Part A - 800 mg AZD9977 (Split Doses) | Apparent Clearance (CL/F) | 29.38 L/h | Standard Deviation 8.43 |
| Part A - 1200 mg AZD9977 (Split Doses) | Apparent Clearance (CL/F) | 45.97 L/h | Standard Deviation 13.03 |
| Part B | Apparent Clearance (CL/F) | 31.82 L/h | Standard Deviation 10.79 |
Secondary
Apparent Volume of Distribution (Vz/F)
To assess plasma pharmacokinetic parameters following single ascending doses of AZD977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Apparent Volume of Distribution (Vz/F) | 61.50 L | Standard Deviation 9.724 |
| Part A - 5 mg AZD9977 | Apparent Volume of Distribution (Vz/F) | 64.52 L | Standard Deviation 13.4 |
| Part A - 25 mg AZD9977 | Apparent Volume of Distribution (Vz/F) | 266.1 L | Standard Deviation 180.6 |
| Part A - 100 mg AZD9977 | Apparent Volume of Distribution (Vz/F) | 315.8 L | Standard Deviation 111.9 |
| Part A - 200 mg AZD9977 | Apparent Volume of Distribution (Vz/F) | 401.9 L | Standard Deviation 180 |
| Part A - 400 mg AZD9977 | Apparent Volume of Distribution (Vz/F) | 1712 L | Standard Deviation 123.7 |
| Part A - 800 mg AZD9977 | Apparent Volume of Distribution (Vz/F) | 652.5 L | Standard Deviation 414 |
| Part A - 800 mg AZD9977 (Split Doses) | Apparent Volume of Distribution (Vz/F) | 897.0 L | Standard Deviation 210.6 |
| Part A - 1200 mg AZD9977 (Split Doses) | Apparent Volume of Distribution (Vz/F) | 720.1 L | Standard Deviation 348.2 |
| Part B | Apparent Volume of Distribution (Vz/F) | 269.4 L | Standard Deviation 142.2 |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t)
To assess plasma pharmacokinetic parameters following single ascending doses of AZD977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 482.7 h.nmol/L | Geometric Coefficient of Variation 14.9 |
| Part A - 5 mg AZD9977 | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 2429 h.nmol/L | Geometric Coefficient of Variation 24.7 |
| Part A - 25 mg AZD9977 | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 9419 h.nmol/L | Geometric Coefficient of Variation 52.2 |
| Part A - 100 mg AZD9977 | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 23470 h.nmol/L | Geometric Coefficient of Variation 34.2 |
| Part A - 200 mg AZD9977 | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 35650 h.nmol/L | Geometric Coefficient of Variation 26 |
| Part A - 400 mg AZD9977 | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 34190 h.nmol/L | Geometric Coefficient of Variation 16.1 |
| Part A - 800 mg AZD9977 | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 82720 h.nmol/L | Geometric Coefficient of Variation 35.6 |
| Part A - 800 mg AZD9977 (Split Doses) | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 93750 h.nmol/L | Geometric Coefficient of Variation 37.5 |
| Part A - 1200 mg AZD9977 (Split Doses) | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 1754 h.nmol/L | Geometric Coefficient of Variation 38.1 |
| Part B | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) | 3136 h.nmol/L | Geometric Coefficient of Variation 31.5 |
Secondary
Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity.
To assess plasma pharmacokinetic parameters following single ascending doses of AZD977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 514.4 h.nmol/L | Geometric Coefficient of Variation 13.4 |
| Part A - 5 mg AZD9977 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 2473 h.nmol/L | Geometric Coefficient of Variation 24.5 |
| Part A - 25 mg AZD9977 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 9576 h.nmol/L | Geometric Coefficient of Variation 51.9 |
| Part A - 100 mg AZD9977 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 23810 h.nmol/L | Geometric Coefficient of Variation 33.7 |
| Part A - 200 mg AZD9977 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 36210 h.nmol/L | Geometric Coefficient of Variation 28.5 |
| Part A - 400 mg AZD9977 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 38060 h.nmol/L | Geometric Coefficient of Variation 37.2 |
| Part A - 800 mg AZD9977 | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 98910 h.nmol/L | Geometric Coefficient of Variation 29.7 |
| Part A - 800 mg AZD9977 (Split Doses) | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 105700 h.nmol/L | Geometric Coefficient of Variation 30.5 |
| Part A - 1200 mg AZD9977 (Split Doses) | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 2256 h.nmol/L | Geometric Coefficient of Variation 32.6 |
| Part B | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. | 3294 h.nmol/L | Geometric Coefficient of Variation 32.9 |
Secondary
Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)]
To assess urine pharmacokinetic parameters following single ascending doses of AZD9977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 2491 nmol | Standard Deviation 213.4 |
| Part A - 5 mg AZD9977 | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 12440 nmol | Standard Deviation 2818 |
| Part A - 25 mg AZD9977 | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 59700 nmol | Standard Deviation 21910 |
| Part A - 100 mg AZD9977 | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 122800 nmol | Standard Deviation 27020 |
| Part A - 200 mg AZD9977 | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 189700 nmol | Standard Deviation 46420 |
| Part A - 400 mg AZD9977 | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 178600 nmol | Standard Deviation 32530 |
| Part A - 800 mg AZD9977 | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 428600 nmol | Standard Deviation 93430 |
| Part A - 800 mg AZD9977 (Split Doses) | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] | 503400 nmol | Standard Deviation 132300 |
Secondary
Fraction Excreted Unchanged in Urine[Fe (0-48)]
To assess percentage of the total drug excreted in the urine that was unchanged following single ascending doses of AZD9977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 19.90 Percentage | Standard Deviation 1.705 |
| Part A - 5 mg AZD9977 | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 19.88 Percentage | Standard Deviation 4.502 |
| Part A - 25 mg AZD9977 | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 23.84 Percentage | Standard Deviation 8.75 |
| Part A - 100 mg AZD9977 | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 24.53 Percentage | Standard Deviation 5.396 |
| Part A - 200 mg AZD9977 | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 18.94 Percentage | Standard Deviation 4.635 |
| Part A - 400 mg AZD9977 | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 8.917 Percentage | Standard Deviation 1.624 |
| Part A - 800 mg AZD9977 | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 21.40 Percentage | Standard Deviation 4.664 |
| Part A - 800 mg AZD9977 (Split Doses) | Fraction Excreted Unchanged in Urine[Fe (0-48)] | 16.75 Percentage | Standard Deviation 4.402 |
Secondary
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz)
To assess plasma pharmacokinetic parameters following single ascending doses of AZD977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 1.741 Hour (h) | Standard Deviation 0.1753 |
| Part A - 5 mg AZD9977 | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 1.755 Hour (h) | Standard Deviation 0.2923 |
| Part A - 25 mg AZD9977 | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 7.161 Hour (h) | Standard Deviation 4.397 |
| Part A - 100 mg AZD9977 | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 10.00 Hour (h) | Standard Deviation 1.933 |
| Part A - 200 mg AZD9977 | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 9.618 Hour (h) | Standard Deviation 3.412 |
| Part A - 400 mg AZD9977 | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 22.99 Hour (h) | Standard Deviation 6.527 |
| Part A - 800 mg AZD9977 | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 21.17 Hour (h) | Standard Deviation 12.18 |
| Part A - 800 mg AZD9977 (Split Doses) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 21.68 Hour (h) | Standard Deviation 3.495 |
| Part A - 1200 mg AZD9977 (Split Doses) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 11.60 Hour (h) | Standard Deviation 6.081 |
| Part B | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) | 6.145 Hour (h) | Standard Deviation 3.365 |
Secondary
Observed Maximum Concentration (Cmax)
To assess plasma pharmacokinetic parameters following single ascending doses of AZD977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Observed Maximum Concentration (Cmax) | 201.6 nmol/L | Geometric Coefficient of Variation 27.7 |
| Part A - 5 mg AZD9977 | Observed Maximum Concentration (Cmax) | 952.0 nmol/L | Geometric Coefficient of Variation 20.9 |
| Part A - 25 mg AZD9977 | Observed Maximum Concentration (Cmax) | 3367 nmol/L | Geometric Coefficient of Variation 41.3 |
| Part A - 100 mg AZD9977 | Observed Maximum Concentration (Cmax) | 5966 nmol/L | Geometric Coefficient of Variation 40.6 |
| Part A - 200 mg AZD9977 | Observed Maximum Concentration (Cmax) | 7243 nmol/L | Geometric Coefficient of Variation 27.7 |
| Part A - 400 mg AZD9977 | Observed Maximum Concentration (Cmax) | 7149 nmol/L | Geometric Coefficient of Variation 17.2 |
| Part A - 800 mg AZD9977 | Observed Maximum Concentration (Cmax) | 14310 nmol/L | Geometric Coefficient of Variation 29.1 |
| Part A - 800 mg AZD9977 (Split Doses) | Observed Maximum Concentration (Cmax) | 16700 nmol/L | Geometric Coefficient of Variation 29.2 |
| Part A - 1200 mg AZD9977 (Split Doses) | Observed Maximum Concentration (Cmax) | 161.2 nmol/L | Geometric Coefficient of Variation 36.8 |
| Part B | Observed Maximum Concentration (Cmax) | 790.9 nmol/L | Geometric Coefficient of Variation 22.9 |
Secondary
Renal Clearance of Drug From Plasma [CLR (0-48)]
To assess urine pharmacokinetic parameters following single ascending doses of AZD9977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A- Placebo | Renal Clearance of Drug From Plasma [CLR (0-48)] | 5.018 L/h | Standard Deviation 0.5818 |
| Part A - 5 mg AZD9977 | Renal Clearance of Drug From Plasma [CLR (0-48)] | 5.061 L/h | Standard Deviation 1.195 |
| Part A - 25 mg AZD9977 | Renal Clearance of Drug From Plasma [CLR (0-48)] | 6.114 L/h | Standard Deviation 1.533 |
| Part A - 100 mg AZD9977 | Renal Clearance of Drug From Plasma [CLR (0-48)] | 5.230 L/h | Standard Deviation 1.028 |
| Part A - 200 mg AZD9977 | Renal Clearance of Drug From Plasma [CLR (0-48)] | 5.371 L/h | Standard Deviation 0.688 |
| Part A - 400 mg AZD9977 | Renal Clearance of Drug From Plasma [CLR (0-48)] | 5.700 L/h | Standard Deviation 1.097 |
| Part A - 800 mg AZD9977 | Renal Clearance of Drug From Plasma [CLR (0-48)] | 5.274 L/h | Standard Deviation 0.9817 |
| Part A - 800 mg AZD9977 (Split Doses) | Renal Clearance of Drug From Plasma [CLR (0-48)] | 5.319 L/h | Standard Deviation 0.5086 |
Secondary
Time to Maximum Observed Plasma Concentration (t Max)
To assess plasma pharmacokinetic parameters following single ascending doses of AZD977
Time frame: Pre-dose and post-dose upto 48 hrs
Population: The PK analysis set for Part A consisted of all subjects in the safety analysis set who received one dose of AZD9977 and had evaluable PK data. The PK analysis set for Part B consisted of all subjects in the safety analysis set who received at least one dose of AZD9977 and had evaluable PK data in at least one period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A- Placebo | Time to Maximum Observed Plasma Concentration (t Max) | 0.50 Hour (h) |
| Part A - 5 mg AZD9977 | Time to Maximum Observed Plasma Concentration (t Max) | 0.99 Hour (h) |
| Part A - 25 mg AZD9977 | Time to Maximum Observed Plasma Concentration (t Max) | 0.50 Hour (h) |
| Part A - 100 mg AZD9977 | Time to Maximum Observed Plasma Concentration (t Max) | 1.00 Hour (h) |
| Part A - 200 mg AZD9977 | Time to Maximum Observed Plasma Concentration (t Max) | 0.88 Hour (h) |
| Part A - 400 mg AZD9977 | Time to Maximum Observed Plasma Concentration (t Max) | 0.75 Hour (h) |
| Part A - 800 mg AZD9977 | Time to Maximum Observed Plasma Concentration (t Max) | 3.51 Hour (h) |
| Part A - 800 mg AZD9977 (Split Doses) | Time to Maximum Observed Plasma Concentration (t Max) | 3.74 Hour (h) |
| Part A - 1200 mg AZD9977 (Split Doses) | Time to Maximum Observed Plasma Concentration (t Max) | 4.02 Hour (h) |
| Part B | Time to Maximum Observed Plasma Concentration (t Max) | 0.75 Hour (h) |