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

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:

MedlinePlus related topics: Constipation

Drug Information available for: Rifampin

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 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 June 18, 2013