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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 24, 2014