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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01533870
First received: February 13, 2012
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

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


Condition Intervention Phase
Drug Induced Constipation
Drug: NKTR-118
Drug: Rifampin
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, Fixed-sequence, 3-period, 3-treatment, Crossover Study to Assess the Effects of Rifampin on Pharmacokinetics of NKTR-118 in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Description of the pharmacokinetic(PK) profile for NKTR 118 after co administration of Rifampin in terms of area under the concentration-time curve from time zero (predose) 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 13 ] [ Designated as safety issue: No ]
  • Description of the PK profile for NKTR 118 in terms of maximum plasma concentration (Cmax), time to Cmax (tmax), half-life (t1/2λz), apparent terminal rate constant (λz). [ 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 13 ] [ 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 the time of the last measurable 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 13 ] [ 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 [AUC(0-24)]. [ 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 13 ] [ Designated as safety issue: No ]
  • Description of the PK profile for NKTR 118 in terms of apparent oral clearance (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 13 ] [ 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-up (Maximum 27 days) ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: March 2012
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NKTR-118
Single dose NKTR-118 25 mg on Day 1 only
Drug: NKTR-118
Oral 25 mg
Active Comparator: Rifampin
Rifampin 600 mg once daily on Days 4 to 12
Drug: Rifampin
Oral 600 mg
Active Comparator: Rifampin/ NKTR-118
Rifampin 600 mg plus NKTR-118 25 mg on Day 13
Drug: NKTR-118
Oral 25 mg
Drug: Rifampin
Oral 600 mg

Detailed Description:

An Open-label, fixed-sequence, 3-period, 3-treatment, Crossover Study to Assess the Effects of Rifampin on 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, in the opinion of the Investigator, 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: NCT01533870

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: Kelli Craven, 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: NCT01533870     History of Changes
Other Study ID Numbers: D3820C00015
Study First Received: February 13, 2012
Last Updated: December 11, 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
Bioavailability
Plasma AUC and Cmax
Plasma AUC0-t and t1/2λz and tmax

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Rifampin
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014