Open Label, Healthy Volunteers, Bioequivalence Study With Naloxegol

A Phase I, Randomised, Open-label, 3 Way Cross-over Study in Healthy Volunteers to Demonstrate the Bioequivalence of the Naloxegol 25 mg Commercial and Phase III Formulations and to Assess the Effect of Food Administration on the Pharmacokinetics of the Commercial Formulation.

The purpose of this study is to demonstrate the Bioequivalence, assess food administration on the Pharmacokinetics with naloxegol.

Study Overview

• Status: Completed
• Conditions: Opioid Induced Constipation
• Intervention / Treatment: Drug: Naloxegol; Drug: Naloxegol

Detailed Description

A Phase I, Randomised, Open-label, 3 way Cross-over Study in Healthy Volunteers to Demonstrate the Bioequivalence of the Naloxegol 25 mg Commercial and Phase III Formulations and to Assess the Effect of Food Administration on the Pharmacokinetics of the Commercial Formulation.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female non-pregnant, non-lactating.
• Volunteers with suitable veins for cannulation or repeated venipuncture.
• Male healthy volunteers should be willing to use barrier contraception ie, condoms, from the first day of dosing until 3 months after dosing with the investigational product.
• The female partner should use contraception during this period.

Exclusion Criteria:

• History of any clinically significant disease or disorder.
• Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of investigational product.
• Volunteers who have smoked or used nicotine products within the previous 3 months from the date of screening.
• Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results as judged by the Investigator .

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Naloxol IR tablet 25 mg (naloxegol oxalate) commercial formulation under fasted conditions	Drug: Naloxegol; Naloxol IR tablet 25 mg (naloxegol oxalate) commercial formulation; Drug: Naloxegol; Naloxegol film-coated Phase III formulation 25 mg film-coated IR tablet
Experimental: B; Naloxol IR tablet 25 mg (naloxegol oxalate) commercial formulation under fed conditions	Drug: Naloxegol; Naloxol IR tablet 25 mg (naloxegol oxalate) commercial formulation; Drug: Naloxegol; Naloxegol film-coated Phase III formulation 25 mg film-coated IR tablet
Experimental: C; Naloxegol film-coated IR tablet 25 mg Phase III formulation under fasted conditions	Drug: Naloxegol; Naloxol IR tablet 25 mg (naloxegol oxalate) commercial formulation; Drug: Naloxegol; Naloxegol film-coated Phase III formulation 25 mg film-coated IR tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Description of the pharmacokinetic (PK) profile for naloxegol in terms of maximum observed plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC) for each treatment period.	Predose,0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours

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 (CSSRS)	From baseline day 1 through to Follow-up (Maximum 40 days)
Description of the pharmacokinetic(PK) profile for naloxegol in terms of time to Cmax (tmax), terminal half-life (t1/2λz), terminal rate constant (λz). For each treatment period	Predose,0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours
Description of the pharmacokinetic (PK) profile for naloxegol in terms of area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)].For each treatment period	Predose,0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours
Description of the pharmacokinetic (PK) profile for naloxegol in terms of area under the plasma concentration-time curve from time zero to 24 hours [AUC(0-24)], apparent oral clearance from plasma (CL/F).For each treatment period	Predose,0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours
Description of the pharmacokinetic (PK) profile for naloxegol in terms of apparent volume of distribution during the terminal phase (Vz/F)For each treatment period	Predose,0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, and 48 hours

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Mark Sostek, MD, Astrazeneca Wilmington, US; Principal Investigator: Arpeat Kaviya, MBCHB, MRCP, Quintiles London UK; Study Chair: Bo Fransson, MD, Astrazeneca Sodertalje Sweden

Publications and helpful links

Helpful Links

• Clinical_Study_Report_Synopsis_D3820C00018

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 18, 2012
• First Submitted That Met QC Criteria: June 19, 2012
• First Posted (Estimate): June 20, 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: Healthy volunteers; Bioequivalence; Phase 1; Naloxegol
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Opioid-Induced Constipation; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxegol
• Other Study ID Numbers: D3820C00018