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

Purpose

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

Condition	Intervention	Phase
Bioavailability Healthy Volunteers Drug- Drug Interactions	Drug: NKTR-118 Drug: Ketoconazole	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Drug Reactions

Drug Information available for: Ketoconazole

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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). [ Time Frame: 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 ] [ Designated as safety issue: No ]
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)]. [ Time Frame: 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 ] [ Designated as safety issue: No ]
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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
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) [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 [ Time Frame: From baseline day 1 through to Follow-u (Maximum 21 days) ] [ Designated as safety issue: Yes ]

Enrollment:	22
Study Start Date:	February 2012
Study Completion Date:	April 2012
Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Part 1 - A Single dose NKTR-118 25 mg on Day 1 only	Drug: NKTR-118 Oral 25 mg
Active Comparator: Part 1 - B Ketoconazole 400 mg once daily on Days 4 to 8	Drug: Ketoconazole Oral 400 mg
Active Comparator: Part 1- C Ketoconazole 400 mg plus NKTR-118 25 mg on Day 7	Drug: NKTR-118 Oral 25 mg Drug: Ketoconazole Oral 400 mg

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

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520896

Locations

United States, Kansas
Research Site
Overland Park, Kansas, United States

Sponsors and Collaborators

AstraZeneca

Investigators

Study Chair:	Bo Fransson, MD	AstraZeneca, Sodertalje Sweden
Principal Investigator:	David Matthews, MD	Quintiles, Inc Kansas Overland Park US.
Study Director:	Mark Sostek, MD	AstraZeneca, Wilmington US

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01520896 History of Changes
Other Study ID Numbers:	D3820C00012
Study First Received:	January 26, 2012
Last Updated:	May 7, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

Phase 1
Healthy male and female volunteers
Drug-drug interaction
Pharmacokinetics
NKTR-118

Additional relevant MeSH terms:

Ketoconazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013