A Study to Compare the Pharmacokinetics of Different Formulations of AZD9977 and the Influence of Food in Healthy Male Subjects

NCT02560363 | Withdrawn Phase 1

• 2 other identifiers: D6400C000032015-002807-26
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Conditions

Pharmacokinetics; Healthy Male Subjects; Safety; Food Effect

Keywords

AZD9977; Safety; Tolerability; Pharmacokinetics; Food effect; AZD9977 capsules; AZD9977 suspension

Outcome Measures

Primary Outcomes (8)

• Rate and extent of absorption of the extended-release formulations in comparison with an immediate-release formulation of AZD9977 by assessment of Frel (AUC)

  Relative bioavailability (Frel \[AUC\]) by assessement of the ratio of AUC (Area under plasma concentration-time curve from time zero extrapolated to infinity) between the extended-release formulations in comparison with an immediate-release formulation of AZD9977

  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

• 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)

  Relative bioavailability (Frel \[AUC0-t\]) by assessement of the ratio of AUC (Area under the plasma concentration-curve from time zero to time of last quantifiable concentration) between the extended-release formulations in comparison with an immediate-release formulation of AZD9977

  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

• 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)

  Relative bioavailability (Frel \[AUC0-24\]) by assessement of the ratio of AUC (Area under the plasma concentration-time curve from time zero to 24 hours post-dose) between the extended-release formulations in comparison with an immediate-release formulation of AZD9977

  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

• Rate and extent of absorption of the extended-release formulations in comparison with an immediate-release formulation of AZD9977 by assessment of Frel (Cmax)

  Relative bioavailability (Frel \[Cmax\]) by assessement of the ratio of AUC (Observed maximum plasma concentration) between the extended-release formulations in comparison with an immediate-release formulation of AZD9977

  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

• 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)

  Relative bioavailability (Frel \[AUC\]) by assessement of the ratio of AUC (Area under plasma concentration-time curve from time zero extrapolated to infinity) after dosing of an extended-release formulation under fed and fasting conditions

  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

• 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)

  Relative bioavailability (Frel \[AUC0-t\]) by assessement of the ratio of AUC (Area under the plasma concentration-curve from time zero to time of last quantifiable concentration) after dosing of an extended-release formulation under fed and fasting conditions

  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

• 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)

  Relative bioavailability (Frel \[AUC0-24\]) by assessement of the ratio of AUC (Area under the plasma concentration-time curve from time zero to 24 hours post-dose) after dosing of an extended-release formulation under fed and fasting conditions

  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

• 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)

  Relative bioavailability (Frel\[Cmax\]) by assessement of the ratio of AUC (Area under the plasma concentration-time curve from time zero to 24 hours post-dose) after dosing of an extended-release formulation under fed and fasting conditions

  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 (7)

• Safety and tolerabilty of AZD9977 by assessment of the number of adverse events and the number of subjects with adverse events

  From screening to post-study visit, up to 10 weeks

• Safety and tolerabilty of AZD9977 by assessment of cardiac telemetry

  On Day -1 and pre-dose until 24 hours post dose on Day 1

• Safety and tolerabilty of AZD9977 by assessment of blood pressure

  From screening to post-study visit, up to 10 weeks

• Safety and tolerabilty of AZD9977 by assessment of pulse

  From screening to post-study visit, up to 10 weeks

• Safety and tolerability of AZD9977 by assessment of electrocardiogram

  From screening to post-study visit, up to 10 weeks

Study Arms (4)

Treatment sequence 1

EXPERIMENTAL

Period 1:Fast ER formulation of AZD9977 Period 2:Intermediate ER formulation of AZD9977 Period 3:Slow ER formulation of AZD9977 Period 4:IR formulation of AZD9977 Period 5:Fast, intermediate or slow ER formulation with food

Drug: AZD9977 immediate release (IR) oral suspension; Drug: AZD9977 extended release (ER) capsules [fast]; Drug: AZD9977 extended release (ER) capsules [intermediate]; Drug: AZD9977 extended release (ER) capsules [slow]

Treatment sequence 2

EXPERIMENTAL

Period 1:Intermediate ER formulation of AZD9977 Period 2:IR formulation of AZD9977 Period 3:Fast ER formulation of AZD9977 Period 4:Slow ER formulation of AZD9977 Period 5:Fast, intermediate or slow ER formulation with food

Drug: AZD9977 immediate release (IR) oral suspension; Drug: AZD9977 extended release (ER) capsules [fast]; Drug: AZD9977 extended release (ER) capsules [intermediate]; Drug: AZD9977 extended release (ER) capsules [slow]

Treatment sequence 3

EXPERIMENTAL

Period 1:Slow ER formulation of AZD9977 Period 2:Fast ER formulation of AZD9977 Period 3:IR formulation of AZD9977 Period 4:Intermediate ER formulation of AZD9977 Period 5:Fast, intermediate or slow ER formulation with food

Drug: AZD9977 immediate release (IR) oral suspension; Drug: AZD9977 extended release (ER) capsules [fast]; Drug: AZD9977 extended release (ER) capsules [intermediate]; Drug: AZD9977 extended release (ER) capsules [slow]

Treatment sequence 4

EXPERIMENTAL

Period 1:IR formulation of AZD9977 Period 2:Slow ER formulation of AZD9977 Period 3:Intermediate ER formulation of AZD9977 Period 4:Fast ER formulation of AZD9977 Period 5:Fast, intermediate or slow ER formulation with food

Drug: AZD9977 immediate release (IR) oral suspension; Drug: AZD9977 extended release (ER) capsules [fast]; Drug: AZD9977 extended release (ER) capsules [intermediate]; Drug: AZD9977 extended release (ER) capsules [slow]

Interventions

AZD9977 immediate release (IR) oral suspension DRUG

120 mg (4.8 mL x 25 mg/mL) oral suspension, single dose

Treatment sequence 1; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4

AZD9977 extended release (ER) capsules [fast] DRUG

120 mg (2 x 60mg capsules) single dose

Treatment sequence 1; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4

AZD9977 extended release (ER) capsules [intermediate] DRUG

120 mg (2 x 60mg capsules) single dose

Treatment sequence 1; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4

AZD9977 extended release (ER) capsules [slow] DRUG

120 mg (2 x 60mg capsules) single dose

Treatment sequence 1; Treatment sequence 2; Treatment sequence 3; Treatment sequence 4

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Harrow, United Kingdom

Location

MeSH Terms

Interventions

AZD9977; Suspensions; Capsules

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Muna Albayaty, MBChB, MSc, MFPM

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: September 25, 2015
• Study Start: November 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 11, 2016

Record last verified: 2016-01

Locations

GB (1)