Clinical trial NCT01520896: Study in Healthy Volunteers to Investigate the Effects of Ketoconazole on the Pharmacokinetics of NKTR-118
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioavailability
Healthy Volunteers
Drug- Drug Interactions
Keywords: Phase 1
Healthy male and female volunteers
Drug-drug interaction
Pharmacokinetics
NKTR-118
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-01-30
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

Eligibility 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.

Primary outcomes:
measure: 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).
timeFrame: 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
measure: 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)].
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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)
timeFrame: 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 outcomes:
measure: 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
timeFrame: From baseline day 1 through to Follow-u (Maximum 21 days)
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Research Site
state: Kansas
Study officials:
affiliation: AstraZeneca, Sodertalje Sweden
name: Bo Fransson, MD
role: STUDY_CHAIR
affiliation: Quintiles, Inc Kansas Overland Park US.
name: David Matthews, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca, Wilmington US
name: Mark Sostek, MD
role: STUDY_DIRECTOR
References: