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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01533155
First received: February 10, 2012
Last updated: November 20, 2012
Last verified: November 2012
  Purpose

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


Condition Intervention Phase
Drug Induced Constipation
Drug: Nektar 118
Drug: Quinidine
Drug: Quinidine placebo
Drug: Morphine
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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). [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • 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)]. [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • 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)]. [ Time Frame: 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. ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: 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. ] [ Designated as safety issue: No ]

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. [ Time Frame: From baseline up to 21 days. ] [ Designated as safety issue: Yes ]
  • 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) [ Time Frame: Measurments from baseline day -1, and at 0.5, 1, 2, 3, 4, 6, and 24 hours post dose. ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: March 2012
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: NKTR-118/ Quinidine
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 118
Oral 25 mg tablet
Drug: Quinidine
Oral 200 mg tablet
Placebo Comparator: NKTR-118/ Placebo
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 118
Oral 25 mg tablet
Drug: Quinidine placebo
Oral Tablet
Active Comparator: NKTR-118/ Quinidine/ Morphine
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 118
Oral 25 mg tablet
Drug: Quinidine
Oral 200 mg tablet
Drug: Quinidine placebo
Oral Tablet
Drug: Morphine
10 mg/ml, intravenously
Placebo Comparator: NKTR-118/ Placebo/ Morphine
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 118
Oral 25 mg tablet
Drug: Morphine
10 mg/ml, intravenously

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01533155

Locations
United States, Kansas
Research Site
Overland Park, Kansas, United States
Sponsors and Collaborators
AstraZeneca
Investigators
Principal Investigator: Phil Leese, MD Quintiles Kansas United states
Study Director: Mark Sostek, MD Astrazeneca, Wilmington US
Study Chair: Bo Fransson, MD Astrazeneca, Sodertalje Sweden
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01533155     History of Changes
Other Study ID Numbers: D3820C00011
Study First Received: February 10, 2012
Last Updated: November 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Phase 1
Healthy male and female volunteers
Drug-drug interaction
Pharmacokinetics
NKTR-118

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Morphine
Quinidine
Quinidine gluconate
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Narcotics
Anti-Arrhythmia Agents
Cardiovascular Agents
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Muscarinic Antagonists
Cholinergic Antagonists

ClinicalTrials.gov processed this record on July 26, 2014