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

Primary Purpose

Drug Induced Constipation

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Nektar 118

Quinidine

Quinidine placebo

Morphine

About this trial

This is an interventional basic science trial for Drug Induced Constipation focused on measuring Phase 1, Healthy male and female volunteers, Drug-drug interaction, Pharmacokinetics, NKTR-118

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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 be nonpregnant and nonlactating. Women of childbearing potential must have negative pregnancy test (screening and admission) and be using a highly-effective form of birth control for 3 months before enrollment.
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) which, may put the volunteer at risk of participation in the study, or influence of the ADME of drugs.
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.
History (personal or family) of torsades de pointes, any other polymorphic ventricular tachycardia, long QT syndrome, sudden death or Brugada syndrome, or personal history of sustained (greater than 30 s) monomorphic ventricular tachycardia.
Abnormal vital signs, after 10 minutes supine rest as defined in protocol.

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

NKTR-118/ Quinidine

NKTR-118/ Placebo

NKTR-118/ Quinidine/ Morphine

NKTR-118/ Placebo/ Morphine

Arm Description

One 25-mg NKTR-118 tablet will be administered once with 3 Quinidine 200mg tablets in the morning of period 1 or period 2 (part 1)

One 25-mg NKTR-118 tablet will be administered once with 3 Placebo tablets in the morning of period 1 or period 2 (part 1)

One 25-mg NKTR-118 tablet will be administered with 3 Quinidine 200mg tablets with Morphine inj 5mg/70kg once in the morning on period 3 or period 4 (Part 2)

One 25-mg NKTR-118 tablet will be administered with 3 placebo tables with Morphine inj 5mg/70kg once in the morning of period 3 or period 4 (part 2)

Outcomes

Primary Outcome Measures

Description of the pharmacokinetic (PK) profile for NKTR- 118 in terms of maximum observed plasma concentration (Cmax), time to Cmax (tmax), apparent terminal half-life (t1/2λz).

Description of the PK profile for NKTR- 118 in terms of apparent terminal rate constant (λz), area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC).

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 quantifiable concentration [AUC(0-t)].

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)].

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).

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.

Description of results from pupillary measurements in terms of size change from baseline on both eyes in mm. (Measurements in 4 different conditions: dark, 0.04 lux, 0.4 lux and 4 lux)

Full Information

NCT ID

NCT01533155

First Posted

February 10, 2012

Last Updated

October 13, 2014

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01533155

Brief Title

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

Official Title

A Randomized, 2-Part, Crossover, Single Center Study to Evaluate Effect of Quinidine on the Pharmacokinetics of NKTR-118 and the Concomitant Effect of Quinidine and NKTR-118 on Morphine-induced Miosis

Study Type

Interventional

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Completed

Study Start Date

March 2012 (undefined)

Primary Completion Date

September 2012 (Actual)

Study Completion Date

September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

5. Study Description

Brief Summary

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

Detailed Description

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Drug Induced Constipation

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

214 (Actual)

8. Arms, Groups, and Interventions

Arm Title

NKTR-118/ Quinidine

Arm Type

Active Comparator

Arm Description

One 25-mg NKTR-118 tablet will be administered once with 3 Quinidine 200mg tablets in the morning of period 1 or period 2 (part 1)

Arm Title

NKTR-118/ Placebo

Arm Type

Placebo Comparator

Arm Description

One 25-mg NKTR-118 tablet will be administered once with 3 Placebo tablets in the morning of period 1 or period 2 (part 1)

Arm Title

NKTR-118/ Quinidine/ Morphine

Arm Type

Active Comparator

Arm Description

One 25-mg NKTR-118 tablet will be administered with 3 Quinidine 200mg tablets with Morphine inj 5mg/70kg once in the morning on period 3 or period 4 (Part 2)

Arm Title

NKTR-118/ Placebo/ Morphine

Arm Type

Placebo Comparator

Arm Description

One 25-mg NKTR-118 tablet will be administered with 3 placebo tables with Morphine inj 5mg/70kg once in the morning of period 3 or period 4 (part 2)

Intervention Type

Drug

Intervention Name(s)

Nektar 118

Intervention Description

Oral 25 mg tablet

Intervention Type

Drug

Intervention Name(s)

Quinidine

Intervention Description

Oral 200 mg tablet

Intervention Type

Drug

Intervention Name(s)

Quinidine placebo

Intervention Description

Oral Tablet

Intervention Type

Drug

Intervention Name(s)

Morphine

Intervention Description

10 mg/ml, intravenously

Primary Outcome Measure Information:

Title

Description of the pharmacokinetic (PK) profile for NKTR- 118 in terms of maximum observed plasma concentration (Cmax), time to Cmax (tmax), apparent terminal half-life (t1/2λz).

Time Frame