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

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ClinicalTrials.gov Identifier: NCT01520896
Recruitment Status : Completed
First Posted : January 30, 2012
Last Update Posted : October 15, 2014
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Bioavailability Healthy Volunteers Drug- Drug Interactions Drug: NKTR-118 Drug: Ketoconazole Phase 1

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (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
Study Start Date : February 2012
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]

Secondary Outcome Measures :
  1. 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) ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01520896     History of Changes
Other Study ID Numbers: D3820C00012
First Posted: January 30, 2012    Key Record Dates
Last Update Posted: October 15, 2014
Last Verified: October 2014

Keywords provided by AstraZeneca:
Phase 1
Healthy male and female volunteers
Drug-drug interaction
Pharmacokinetics
NKTR-118

Additional relevant MeSH terms:
Ketoconazole
Naloxegol
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Narcotic Antagonists
Sensory System Agents
Peripheral Nervous System Agents