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

NCT01520896 | Completed Phase 1

• 1 other identifier: D3820C00012
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Bioavailability; Healthy Volunteers; Drug- Drug Interactions

Keywords

Phase 1; Healthy male and female volunteers; Drug-drug interaction; Pharmacokinetics; NKTR-118

Outcome Measures

Primary Outcomes (4)

• 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).

  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

• 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)].

  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

• 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

  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

• 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)

  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 Outcomes (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

  From baseline day 1 through to Follow-u (Maximum 21 days)

Study Arms (3)

Part 1 - A

EXPERIMENTAL

Single dose NKTR-118 25 mg on Day 1 only

Drug: NKTR-118

Part 1 - B

ACTIVE COMPARATOR

Ketoconazole 400 mg once daily on Days 4 to 8

Drug: Ketoconazole

Part 1- C

ACTIVE COMPARATOR

Ketoconazole 400 mg plus NKTR-118 25 mg on Day 7

Drug: NKTR-118; Drug: Ketoconazole

Interventions

NKTR-118 DRUG

Oral 25 mg

Part 1 - A; Part 1- C

Ketoconazole DRUG

Oral 400 mg

Part 1 - B; Part 1- C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Overland Park, Kansas, United States

Location

Related Links

• D3820C00012 Clinical Study Report Synopsis

MeSH Terms

Interventions

naloxegol; Ketoconazole

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Bo Fransson, MD

  AstraZeneca, Sodertalje Sweden

  STUDY CHAIR

• David Matthews, MD

  Quintiles, Inc Kansas Overland Park US.

  PRINCIPAL INVESTIGATOR

• Mark Sostek, MD

  AstraZeneca, Wilmington US

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2012
• First Posted: January 30, 2012
• Study Start: February 1, 2012
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: October 15, 2014

Record last verified: 2014-10

Locations

US (1)