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

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

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

Study Overview

• Status: Completed
• Conditions: Drug Induced Constipation
• Intervention / Treatment: Drug: NKTR-118; Drug: Rifampin

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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).	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
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).	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
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)].	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
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)].	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
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).	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

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	From baseline day -1 through to Follow-up (Maximum 27 days)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Kelli Craven, MD, Quintiles, Inc Kansas Overland Park US.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: February 13, 2012
• First Submitted That Met QC Criteria: February 14, 2012
• First Posted (Estimate): February 15, 2012

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase 1; Bioavailability; Drug-drug interaction; NKTR-118; Healthy male and female volunteers; Plasma AUC and Cmax; Plasma AUC0-t and t1/2λz and tmax
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Sensory System Agents; Anti-Bacterial Agents; Narcotic Antagonists; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Naloxegol
• Other Study ID Numbers: D3820C00015