A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD9977 After Single Ascending Doses to Healthy Males
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT02484729
Collaborator
(none)
196
1
3
4
48.5
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
196 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Basic Science
Official Title:
A Phase I, Randomized, Single-blind, Placebo-controlled Study to Access the Safety, Tolerability and Pharmacokinetics of AZD9977 Following Single Ascending Dose Administration to Healthy Male Subjects
Study Start Date
:
Jul 1, 2015
Actual Primary Completion Date
:
Nov 1, 2015
Actual Study Completion Date
:
Nov 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AZD9977 oral suspension, single doses In Part A up to 10 cohorts with single ascending doses with AZD9977 as oral suspension. In Part B AZD9977 as oral suspension in IntelliCap® capsule |
Drug: AZD9977, 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)
|
| Placebo Comparator: Placebo, oral suspension, single doses In Part A up to 10 cohorts with single doses with matching placebo to AZD9977 |
Drug: Placebo, oral suspension
Matching placebo
|
| Experimental: AZD9977, oral solution, single dose In Part B, of oral solution of AZD9977 will be used as reference |
Drug: AZD9977, oral solution
AZD9977, single dose of oral solution in Part B as reference
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
- 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
- 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
- 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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 50 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Provision of signed and dated written informed consent prior to any study specific procedures.
-
Healthy male subjects aged 18 to 50 years with suitable veins for cannulation or repeated venipuncture.
-
Male subjects have to comply with the restrictions for sexual activity provided to them.
-
Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
-
Optional: Provision of signed and dated written informed consent for genetic research.
If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
- Able to understand, read and speak the English language.
Exclusion Criteria:
-
History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study.
-
History or presence of GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
-
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of dosing in Part A or the first dose of AZD9977 in Part B.
-
Any clinically significant abnormalities in hematology, clinical chemistry or urinalysis results, as judged by the investigator.
-
Any positive result at screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibodies.
-
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
-
Any clinically important abnormalities in rhythm, conduction or morphology of the electrocardiogram (ECG) at screening or pre-dose, as considered by the investigator.
-
Prolonged QTcF > 450 ms or family history of long QT syndrome.
-
PR (PQ) interval shortening < 120 ms. PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation.
-
PR (PQ) interval prolongation > 240ms; intermittent second or third degree atrioventricular (AV) block, or AV dissociation.
Wenckebach block while asleep is not exclusive.
- 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.
-
Serum potassium higher than 5.0 mmol/L at screening or admission to the study center (Day -1).
-
Known or suspected history of drug abuse as judged by the investigator.
-
Current smokers or those who have smoked or used nicotine products within the previous 3 months.
-
History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
-
Positive screen for drugs of abuse, alcohol or cotinine at screening or admission to the study center.
-
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.
-
Excessive intake of caffeine containing drinks or food (e.g., coffee, tea and chocolate) as judged by the investigator.
-
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.
-
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.
-
Plasma donation within one month of screening or any blood donation/blood loss > 500 mL during the 3 months prior to screening.
-
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.
-
Involvement of any AstraZeneca or study site employee or their close relatives.
-
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.
-
Subjects who are vegans or have medical dietary restrictions (vegetarians may be included in the study).
-
Subjects who cannot communicate reliably with the investigator.
-
Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
-
Previous bone marrow transplant.
-
Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Criteria applicable to Part B only:
-
Subjects with pacemakers or other implanted electro-medical devices.
-
Subjects with swallowing disorders.
-
Subjects with pre-planned MRI examination.
-
Subjects not willing to have an abdominal X-ray performed if the IntelliCap® capsule has not been retrieved within one week after ingestion.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Harrow | United Kingdom |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Principal Investigator: Muna Albayaty, Dr., PAREXEL Early Phase Clinical Unit London, Level 7, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, United Kingdom
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02484729
Other Study ID Numbers:
- D6400C00001
- 2015-000877-11
First Posted:
Jun 30, 2015
Last Update Posted:
Apr 28, 2017
Last Verified:
Mar 1, 2017
Keywords provided by AstraZeneca
Study Results
Participant Flow
| Recruitment Details | This study was conducted at PAREXEL International, Early Phase Clinical Unit London, United Kingdom. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Period Title: Overall Study | ||||||||||
| STARTED | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| COMPLETED | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 7 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | Total of all reporting groups |
| Overall Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 | 70 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||||
| Mean (Standard Deviation) [Years] |
30
(6)
|
32
(11)
|
30
(9)
|
36
(10)
|
32
(10)
|
33
(9)
|
30
(6)
|
32
(8)
|
38
(11)
|
35
(9)
|
33
(9)
|
| Sex/Gender, Customized (Number) [Number] | |||||||||||
| Male |
16
100%
|
6
100%
|
6
100%
|
6
100%
|
5
100%
|
6
100%
|
5
100%
|
6
100%
|
6
100%
|
8
100%
|
70
100%
|
Outcome Measures
| Title | Safety and Tolerability of AZD9977 by Assessing the Percentage of Participants With Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [percentage of participants] |
43.8
273.8%
|
16.7
278.3%
|
33.3
555%
|
33.3
555%
|
20.0
400%
|
33.3
555%
|
0
0%
|
33.3
555%
|
16.7
278.3%
|
37.5
468.8%
|
| Title | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Pulse Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Trends in 12-lead Electrocardiograms |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Safety and Tolerability of AZD9977 by Number of Participants With Clinically Significant Trends in Cardiac Telemetry |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Safety and Tolerability of AZD9977 by Assessing the Number of Subjects With Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of Participants] |
7
43.8%
|
1
16.7%
|
2
33.3%
|
2
33.3%
|
1
20%
|
2
33.3%
|
0
0%
|
2
33.3%
|
1
16.7%
|
3
37.5%
|
| Title | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Blood Pressure |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Hematology |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Clinical Chemistry |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Safety and Tolerability of AZD9977 by Assessing Number of Participants With Clinically Significant Changes in Urinalysis |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 |
| Measure Participants | 16 | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 8 |
| Number [Number of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Area Under the Plasma Concentration Versus Time Curve (AUC) From Zero Extrapolated to Infinity. |
|---|---|
| Description | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) | Intellicap Device (Part B) | Oral Suspension (Part B) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | 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 |
| Measure Participants | 6 | 6 | 6 | 5 | 5 | 2 | 5 | 4 | 4 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [h.nmol/L] |
514.4
(13.4)
|
2473
(24.5)
|
9576
(51.9)
|
23810
(33.7)
|
36210
(28.5)
|
38060
(37.2)
|
98910
(29.7)
|
105700
(30.5)
|
2256
(32.6)
|
3294
(32.9)
|
| Title | Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Analyte concentrationAUC(0-t) |
|---|---|
| Description | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) | Intellicap Device (Part B) | Oral Suspension (Part B) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | 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 |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 7 | 6 |
| Geometric Mean (Geometric Coefficient of Variation) [h.nmol/L] |
482.7
(14.9)
|
2429
(24.7)
|
9419
(52.2)
|
23470
(34.2)
|
35650
(26.0)
|
34190
(16.1)
|
82720
(35.6)
|
93750
(37.5)
|
1754
(38.1)
|
3136
(31.5)
|
| Title | Observed Maximum Concentration (Cmax) |
|---|---|
| Description | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) | Intellicap Device (Part B) | Oral Suspension (Part B) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | 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 |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 7 | 7 |
| Geometric Mean (Geometric Coefficient of Variation) [nmol/L] |
201.6
(27.7)
|
952.0
(20.9)
|
3367
(41.3)
|
5966
(40.6)
|
7243
(27.7)
|
7149
(17.2)
|
14310
(29.1)
|
16700
(29.2)
|
161.2
(36.8)
|
790.9
(22.9)
|
| Title | Time to Maximum Observed Plasma Concentration (t Max) |
|---|---|
| Description | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) | Intellicap Device (Part B) | Oral Suspension (Part B) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | 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 |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 6 | 7 | 7 |
| Median (Full Range) [Hour (h)] |
0.50
|
0.99
|
0.50
|
1.00
|
0.88
|
0.75
|
3.51
|
3.74
|
4.02
|
0.75
|
| Title | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) |
|---|---|
| Description | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) | Intellicap Device (Part B) | Oral Suspension (Part B) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | |
| Measure Participants | 6 | 6 | 6 | 5 | 5 | 2 | 5 | 4 | 4 | 7 |
| Mean (Standard Deviation) [Hour (h)] |
1.741
(0.1753)
|
1.755
(0.2923)
|
7.161
(4.397)
|
10.00
(1.933)
|
9.618
(3.412)
|
22.99
(6.527)
|
21.17
(12.18)
|
21.68
(3.495)
|
11.60
(6.081)
|
6.145
(3.365)
|
| Title | Apparent Clearance (CL/F) |
|---|---|
| Description | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) | Intellicap Device (Part B) | Oral Suspension (Part B) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | 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 |
| Measure Participants | 6 | 6 | 6 | 5 | 5 | 2 | 5 | 4 | 4 | 7 |
| Mean (Standard Deviation) [L/h] |
24.52
(3.391)
|
25.89
(5.546)
|
28.46
(11.08)
|
21.84
(5.812)
|
28.49
(7.392)
|
54.34
(19.16)
|
20.99
(6.683)
|
29.38
(8.430)
|
45.97
(13.03)
|
31.82
(10.79)
|
| Title | Apparent Volume of Distribution (Vz/F) |
|---|---|
| Description | To assess plasma pharmacokinetic parameters following single ascending doses of AZD977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) | Intellicap Device (Part B) | Oral Suspension (Part B) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | 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 |
| Measure Participants | 6 | 6 | 6 | 5 | 5 | 2 | 5 | 4 | 4 | 7 |
| Mean (Standard Deviation) [L] |
61.50
(9.724)
|
64.52
(13.40)
|
266.1
(180.6)
|
315.8
(111.9)
|
401.9
(180.0)
|
1712
(123.7)
|
652.5
(414.0)
|
897.0
(210.6)
|
720.1
(348.2)
|
269.4
(142.2)
|
| Title | Cumulative Amount of Unchanged Drug Excreted Into Urine [Ae (0-48)] |
|---|---|
| Description | To assess urine pharmacokinetic parameters following single ascending doses of AZD9977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 5 |
| Mean (Standard Deviation) [nmol] |
2491
(213.4)
|
12440
(2818)
|
59700
(21910)
|
122800
(27020)
|
189700
(46420)
|
178600
(32530)
|
428600
(93430)
|
503400
(132300)
|
| Title | Fraction Excreted Unchanged in Urine[Fe (0-48)] |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 5 |
| Mean (Standard Deviation) [Percentage] |
19.90
(1.705)
|
19.88
(4.502)
|
23.84
(8.750)
|
24.53
(5.396)
|
18.94
(4.635)
|
8.917
(1.624)
|
21.40
(4.664)
|
16.75
(4.402)
|
| Title | Renal Clearance of Drug From Plasma [CLR (0-48)] |
|---|---|
| Description | To assess urine pharmacokinetic parameters following single ascending doses of AZD9977 |
| Time Frame | Pre-dose and post-dose upto 48 hrs |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions |
| Measure Participants | 6 | 6 | 6 | 5 | 6 | 5 | 6 | 5 |
| Mean (Standard Deviation) [L/h] |
5.018
(0.5818)
|
5.061
(1.195)
|
6.114
(1.533)
|
5.230
(1.028)
|
5.371
(0.6880)
|
5.700
(1.097)
|
5.274
(0.9817)
|
5.319
(0.5086)
|
Adverse Events
| Time Frame | SAEs will be collected from the signing of informed consent and AEs from randomization until the final follow-up visit in Part A, and from first dosing until the final follow-up visit in Part B. | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||||
| Arm/Group Title | 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 | ||||||||||
| Arm/Group Description | Subjects received matching placebo under fasted conditions | Subjects received 5 mg AZD9977, oral suspension under fasted conditions | Subjects received 25 mg AZD9977, oral suspension under fasted conditions | Subjects received 100 mg AZD9977, oral suspension under fasted conditions | Subjects received 200 mg AZD9977, oral suspension under fasted conditions | Subjects received 400 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977, oral suspension under fasted conditions | Subjects received 800 mg AZD9977 (split doses), oral suspension under fasted conditions | Subjects received 1200 mg AZD9977 (split doses), oral suspension under fasted conditions | 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 | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| 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 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| 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 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| 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 | |||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/16 (43.8%) | 1/6 (16.7%) | 2/6 (33.3%) | 2/6 (33.3%) | 1/5 (20%) | 1/6 (16.7%) | 0/5 (0%) | 2/6 (33.3%) | 1/6 (16.7%) | 3/8 (37.5%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal distension | 0/16 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Nausea | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/8 (12.5%) | ||||||||||
| Abdominal discomfort | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/8 (12.5%) | ||||||||||
| Abdominal pain | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/8 (12.5%) | ||||||||||
| Feces soft | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/8 (12.5%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Feeling hot | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Thirst | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Nasopharyngitis | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/8 (25%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Contusion | 2/16 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Face injury | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/8 (12.5%) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Backpain | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Musculoskeletal pain | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Myalgia intercostal | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Dizziness | 1/16 (6.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/6 (0%) | 1/5 (20%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Headache | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/8 (12.5%) | ||||||||||
| Presyncope | 1/16 (6.3%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Psychiatric disorders | ||||||||||||||||||||
| Anxiety | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Hyperhidrosis | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Pruritus | 0/16 (0%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/8 (0%) | ||||||||||
| Skin irritation | 2/16 (12.5%) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/5 (0%) | 0/6 (0%) | 0/6 (0%) | 1/8 (12.5%) | ||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If a publication (e.g., in a scientific journal) based on the results of this study is envisaged, approval from AstraZeneca will be obtained and a draft manuscript will be submitted to AstraZeneca for scrutiny and comment. The choice of conduit will be mutually agreed on by the Principal Investigator and AstraZeneca.
Results Point of Contact
| Name/Title | Global Clinical Leader |
|---|---|
| Organization | AstraZeneca AB |
| Phone | +46 31 7761000 |
| ClinicalTrialTransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02484729
Other Study ID Numbers:
- D6400C00001
- 2015-000877-11
First Posted:
Jun 30, 2015
Last Update Posted:
Apr 28, 2017
Last Verified:
Mar 1, 2017