NCT01533155

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
214

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Mar 2012

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 10, 2012

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 15, 2012

Completed
15 days until next milestone

Study Start

First participant enrolled

March 1, 2012

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2012

Completed
Last Updated

October 15, 2014

Status Verified

October 1, 2014

Enrollment Period

6 months

First QC Date

February 10, 2012

Last Update Submit

October 13, 2014

Conditions

Drug Induced Constipation

Keywords

Phase 1Healthy male and female volunteersDrug-drug interactionPharmacokineticsNKTR-118

Outcome Measures

Primary Outcomes (5)

  • 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).

    At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.

  • 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).

    At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.

  • 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)].

    At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.

  • 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)].

    At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.

  • 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).

    At predose and at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours postdose.

Secondary Outcomes (2)

  • 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 up to 21 days.

  • 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)

    Measurments from baseline day -1, and at 0.5, 1, 2, 3, 4, 6, and 24 hours post dose.

Study Arms (4)

NKTR-118/ Quinidine

ACTIVE COMPARATOR

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)

Drug: Nektar 118Drug: Quinidine

NKTR-118/ Placebo

PLACEBO COMPARATOR

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)

Drug: Nektar 118Drug: Quinidine placebo

NKTR-118/ Quinidine/ Morphine

ACTIVE COMPARATOR

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)

Drug: Nektar 118Drug: QuinidineDrug: Quinidine placeboDrug: Morphine

NKTR-118/ Placebo/ Morphine

PLACEBO COMPARATOR

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)

Drug: Nektar 118Drug: Morphine

Interventions

Nektar 118DRUG

Oral 25 mg tablet

NKTR-118/ PlaceboNKTR-118/ Placebo/ MorphineNKTR-118/ QuinidineNKTR-118/ Quinidine/ Morphine
QuinidineDRUG

Oral 200 mg tablet

NKTR-118/ QuinidineNKTR-118/ Quinidine/ Morphine
Quinidine placeboDRUG

Oral Tablet

NKTR-118/ PlaceboNKTR-118/ Quinidine/ Morphine
MorphineDRUG

10 mg/ml, intravenously

NKTR-118/ Placebo/ MorphineNKTR-118/ Quinidine/ Morphine

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Research Site

Overland Park, Kansas, United States

Location

Related Links

MeSH Terms

Interventions

QuinidineMorphine

Intervention Hierarchy (Ancestors)

Cinchona AlkaloidsAlkaloidsHeterocyclic CompoundsQuinuclidinesHeterocyclic Compounds, Bridged-RingQuinolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingMorphine DerivativesMorphinansOpiate AlkaloidsHeterocyclic Compounds, 4 or More RingsPhenanthrenesPolycyclic Aromatic HydrocarbonsPolycyclic Compounds

Study Officials

  • Phil Leese, MD

    Quintiles Kansas United states

    PRINCIPAL INVESTIGATOR

  • Mark Sostek, MD

    Astrazeneca, Wilmington US

    STUDY DIRECTOR

  • Bo Fransson, MD

    Astrazeneca, Sodertalje Sweden

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 10, 2012

First Posted

February 15, 2012

Study Start

March 1, 2012

Primary Completion

September 1, 2012

Study Completion

September 1, 2012

Last Updated

October 15, 2014

Record last verified: 2014-10

Locations

US(1)