Study in Healthy Volunteers to Investigate the Effects of Ketoconazole on the Pharmacokinetics of NKTR-118

Phase 1

Completed

• Conditions: Drug- Drug Interactions; Bioavailability; Healthy Volunteers
• Interventions: Drug: NKTR-118; Drug: Ketoconazole

• Registration Number: NCT01520896
• Lead Sponsor: AstraZeneca

Brief Summary

Study in healthy volunteers to investigate the effects of Ketoconazole on the Pharmacokinetics of NKTR-118

Detailed Description

An Open-label, 1-sequence, 3-period, 3-treatment, Crossover Study to Assess the Effects of Ketoconazole on the Pharmacokinetics of NKTR-118 in Healthy Subjects

Study Timeline

• Study First Submitted: 2012-01-26
• Study First Submitted QC: 2012-01-26
• Study First Posted: 2012-01-30
• Study Start: 2012-02
• Primary Completion: 2012-04
• Study Completion: 2012-04
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-13
• Last Update Posted: 2014-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Male and female (nonchildbearing potential, nonlactating)healthy volunteers aged 18 to 55 years inclusive, with suitable veins for cannulation or repeated venipuncture.
• Female volunteers must have a negative pregnancy test at screening and at admission, must not be lactating, and must be of nonchildbearing potential.
• Male volunteers should be willing to use barrier contraception ie, condoms, from the first day of dosing until 3 months after dosing with the IP. The female partner should use contraception during this period.
• Volunteers must have a BMI between 18 and 30 kg/m2, inclusive, and weigh at least 50 kg.

Exclusion Criteria

• Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, or major physical impairment), as judged by the Investigator.
• Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IP.
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results as judged by the Investigator.
• Significant orthostatic reaction at enrollment as judged by the Investigator.
• Abnormal vital signs, after 10 minutes supine rest as defined in protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Part 1- C	NKTR-118	Ketoconazole 400 mg plus NKTR-118 25 mg on Day 7
Part 1 - A	NKTR-118	Single dose NKTR-118 25 mg on Day 1 only
Part 1 - B	Ketoconazole	Ketoconazole 400 mg once daily on Days 4 to 8
Part 1- C	Ketoconazole	Ketoconazole 400 mg plus NKTR-118 25 mg on Day 7

Primary Outcome Measures

Name	Time	Method
Description of the PK profile for NKTR 118 in terms of apparent terminal rate constant (?z), area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)].	Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7
Description of the pharmacokinetic(PK) profile for NKTR 118 after co administration of Ketaconazole in terms of maximum observed plasma concentration (Cmax), time to Cmax (tmax), apparent terminal half-life (t1/2?z).	Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7
Description of the PK profile for NKTR 118 in terms of area under the plasma concentration-time curve from time zero to 24 hours postdose [AUC(0 24)], area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC	Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7
Description of the PK profile for NKTR 118 in terms of apparent oral clearance from plasma (CL/F), and apparent volume of distribution during the terminal phase (Vz/F)	Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7

Secondary Outcome Measures

Name	Time	Method
Description of the safety profile in terms of adverse events, clinical laboratory assessments , vital signs (blood pressure and pulse rate), physical examinations, electrocardiograms, and Columbia-Suicide Severity Rating scale	From baseline day 1 through to Follow-u (Maximum 21 days)

Trial Locations

Locations (1)

Research Site; 🇺🇸 Overland Park, Kansas, United States