Clinical trial NCT02560363: A Study to Compare the Pharmacokinetics of Different Formulations of AZD9977 and the Influence of Food in Healthy Male Subjects
Official title: An Open-label, Randomized, Cross Over Single Oral Dose Study Comparing the Pharmacokinetics of Different Formulations of AZD9977 (Part A) and Influence of Food (Part B) in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Pharmacokinetics
Healthy Male Subjects
Safety
Food Effect
Keywords: AZD9977
Safety
Tolerability
Pharmacokinetics
Food effect
AZD9977 capsules
AZD9977 suspension
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-09-25
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This is an open-label, randomized, cross over single oral dose study to compare the pharmacokinetics of different formulations of AZD9977 in Part A and the influence of food in Part B in healthy male subjects

Detailed description: This is an open-label, randomized, cross over single oral dose study to compare the pharmacokinetics of three different extended-release formulations and an immediate-release formulation (reference) of AZD9977 in Part A and the influence of food in Part B in healthy male subjects

Eligibility criteria: 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 32 kg/m2, inclusive, and weigh at least 50 kg.
* Subject judged likely to complete and agree to eat a specified high-fat, high-calorie standardized FDA breakfast.
* 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 volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
* History or presence of gastrointestinal (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 the first administration of IMP.
* Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis results, as judged by the investigator.
* Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody.
* 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 \> 240 ms; intermittent second (history of Wenckebach block while asleep is not exclusive) or third degree atrioventricular (AV) block or AV dissociation.
* Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB) or intraventricular conduction delay (IVCD) with QRS \> 110 ms. Subjects with 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 3 months prior to screening.
* 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 first dose of AZD9977.
* 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 1st dosing in Part A, or longer if the medication has a long half-life.
* Plasma donation within 1 month of screening or any blood donation/loss more than 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 the first administration of IMP in this study. The period of exclusion begins 3 months after the final dose or 1 month after the last visit whichever is the longest.
* Subjects who have previously received AZD9977
* Involvement of any AstraZeneca, PAREXEL, 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, vegetarians or have medical dietary restrictions.
* 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.

Primary outcomes:
measure: Rate and extent of absorption of the extended-release formulations in comparison with an immediate-release formulation of AZD9977 by assessment of Frel (AUC)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
measure: Rate and extent of absorption of the extended-release formulations in comparison with an immediate-release formulation of AZD9977 by assessment of Frel (AUC0-t)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
measure: Rate and extent of absorption of the extended-release formulations in comparison with an immediate-release formulation of AZD9977 by assessment of Frel (AUC0-24)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
measure: Rate and extent of absorption of the extended-release formulations in comparison with an immediate-release formulation of AZD9977 by assessment of Frel (Cmax)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
measure: Rate and extent of absorption of an extended-release formulation of AZD9977 under fasting condtions in comparision with fed condtions by assessment of Frel (AUC)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
measure: Rate and extent of absorption of an extended-release formulation of AZD9977 under fasting condtions in comparision with fed condtions by assessment of Frel(AUC0-t)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
measure: Rate and extent of absorption of an extended-release formulation of AZD9977 under fasting condtions in comparision with fed condtions by assessment of Frel(AUC0-24)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
measure: Rate and extent of absorption of an extended-release formulation of AZD9977 under fasting condtions in comparision with fed condtions by assessment of Frel(Cmax)
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 28, 32, 36 and 48 hours post-dose on each dosing day
Secondary outcomes:
measure: Safety and tolerabilty of AZD9977 by assessment of the number of adverse events and the number of subjects with adverse events
timeFrame: From screening to post-study visit, up to 10 weeks
measure: Safety and tolerabilty of AZD9977 by assessment of cardiac telemetry
timeFrame: On Day -1 and pre-dose until 24 hours post dose on Day 1
measure: Safety and tolerabilty of AZD9977 by assessment of blood pressure
timeFrame: From screening to post-study visit, up to 10 weeks
measure: Safety and tolerabilty of AZD9977 by assessment of pulse
timeFrame: From screening to post-study visit, up to 10 weeks
measure: Safety and tolerability of AZD9977 by assessment of electrocardiogram
timeFrame: From screening to post-study visit, up to 10 weeks
measure: Safety and tolerability of AZD9977 by assessment of physical examination
timeFrame: From screening to post-study visit, up to 10 weeks
measure: Safety and tolerability of AZD9977 by assessment of safety laboratory tests
timeFrame: From screening to post-study visit, up to 10 weeks
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Parexel
name: Muna Albayaty, MBChB, MSc, MFPM
role: PRINCIPAL_INVESTIGATOR
References: