Assessment of Relative Bioavailability of NKTR-118 in Three Formulations in Healthy Subjects

A Phase I, Open-label, Randomized, Balanced, Single-dose, Two-Part Study to Assess the Relative Bioavailability of NKTR-118 in Three Formulations Under Fasted (3-Way Crossover) and Fed (2-Way Crossover) Conditions in Male and Non-fertile Female Subjects

The is an assessment of Relative Bioavailability of NKTR-118 in Three Formulations in Healthy Subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: NKTR118 Formulation 1; Drug: NKTR118 Formulation 2; Drug: NKTR118 Formulation 3; Drug: NKTR118 Formulation 1a; Drug: NKTR118 Formulation 3a

• Study Type: Interventional
• Enrollment (Actual): 21
• 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
• Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating, and must be of non-childbearing potential, confirmed at screening by fulfilling one of the following criteria:
• Post-menopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and with follicle stimulating hormone (FSH) levels in the laboratory defined post-menopausal range
• Irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation
• Volunteers must have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg
• Volunteers must be able to understand and be willing to comply with study procedures, restrictions and requirements
• Healthy male and non-fertile female volunteers ages 18 to 55 years inclusive, with suitable veins for cannulation or repeated venipuncture

Exclusion Criteria:

• Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment) which, in the opinion of the Investigator, may either put the healthy volunteer at risk because of participation in the study, or influence the absorption, distribution, metabolism, and excretion of drugs
• Current smokers, those who have smoked or used nicotine products within the previous 3 months from the date of screening (Visit 1)
• Plasma donation within 1 month of screening or any blood donation/blood loss >500 mL during the 3 months prior to screening or intention to donate blood or blood products during the study or within 3 months after the completion of the study
• Positive screen for drugs of abuse, or cotinine (nicotine level above 400 ng/mL), at screening or admission and/or positive alcohol test at admission
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NKTR118 Formulation 1; Fasted	Drug: NKTR118 Formulation 1; Oral dose, 25 mg
Experimental: NKTR118 Formulation 2; Fasted	Drug: NKTR118 Formulation 2; Oral dose, 25 mg
Experimental: NKTR118 Formulation 3; Fasted	Drug: NKTR118 Formulation 3; Oral dose, 25 mg
Experimental: NKTR118 Formulation 1a; Fed	Drug: NKTR118 Formulation 1a; Oral dose, 25 mg
Experimental: NKTR118 Formulation 3a; FED	Drug: NKTR118 Formulation 3a; Oral dose, 25 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics after a dose of NKTR-118 25 mg by assessment of (Cmax)	day-1 to day 3
Pharmacokinetics after a dose of NKTR-118 25 mg by assessment of time to Cmax (tmax)	day-1 to day 3
Pharmacokinetics after a dose of NKTR-118 25 mg by assessment of half-life (t1/2λz)	day-1 to day 3
Pharmacokinetics after a dose of NKTR-118 25 mg by assessment of area under concentration-time curve (AUC(0-t))	day-1 to day 3
Pharmacokinetics after a dose of NKTR-118 25 mg by assessment of area from time zero (pre-dose) extrapolated to infinity (AUC).	day-1 to day 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of NKTR-118 following administration of a single oral doses of NKTR-118 of 3 different formulations during fed and fasted conditions by assessing adverse events	Duration day -1 (Visit 2) to follow up (Visit 12)
Safety and tolerability of NKTR-118 following administration of a single oral doses of NKTR-118 of 3 different formulations during fed and fasted conditions by assessing Safety Laboratory values	Duration day -1 (Visit 2) to follow up (Visit 12)
Safety and tolerability of NKTR-118 following administration of a single oral doses of NKTR-118 of 3 different formulations during fed and fasted conditions by assessing 12-Lead Electrocardiograms	Duration day -1 (Visit 2) to follow up (Visit 12)
Safety and tolerability of NKTR-118 following administration of a single oral doses of NKTR-118 of 3 different formulations during fed and fasted conditions by assessing Columbia-Suicide Severity Rating Scale (C-SSRS)	Duration day -1 (Visit 2) to follow up (Visit 12)
Concentration of NKTR-118 in plasma samples after drug intake during Fed condition	Duration: Day 1 to day 4 at the 2 last inhouse stays

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Mark Sostek, MD, AstraZeneca; Principal Investigator: David Mathews, MD, Quintiles, Inc.

Publications and helpful links

Helpful Links

• D3820C00025 Clinical Study Report Synopsis

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): August 1, 2011

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (Estimate): June 3, 2011

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; tmax; Cmax; NKTR-118; QTcF Interval; AUC(0-t); cross-over study; fasting or fed state
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxegol
• Other Study ID Numbers: D3820C00025