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

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:

MedlinePlus related topics: Constipation

Drug Information available for: Quinidine sulfate Morphine sulfate Quinidine gluconate

U.S. FDA Resources

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

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 May 23, 2013