Clinical Trials/NCT01877226

NCT01877226

Completed

Phase 1

An Open-Label, Sequential Treatment Study to Assess the Single and Multiple Dose Pharmacokinetics of a New Tapentadol Prolonged-Release 250 mg Formulation in Healthy Subjects

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.0 sites18 target enrollmentSeptember 2008

ConditionsHealthy

InterventionsTapentadol

DrugsTapentadol

Overview

Phase: Phase 1
Intervention: Tapentadol
Conditions: Healthy
Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Enrollment: 18
Primary Endpoint: Maximum Serum Concentration (Cmax) of Tapentadol
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate pharmacokinetics (explores what the body does to the drug), safety and tolerability of single and multiple-dose of tapentadol in healthy participants.

Detailed Description

This is an open-label (all people know the identity of the intervention), single-center, Phase 1 and, single and multiple-dose study of tapentadol tamper resistant prolonged-release formulation (TRF) 250 milligram (mg) tablet in healthy participants. The total study duration will be approximately of 29 days per participant. The study consists of 3 parts: Screening (that is, 21 days before study commences on Day 1); Treatment (single-dose of tapentadol on Day 1, and multiple dose from Day 4-6 \[followed by washout period of 24 hours\]); and End-of-study (Day 8). All the eligible participants will receive single oral dose of tapentadol TRF 250 mg on Day 1 and twice daily from Day 4-6 (total 5 doses). Participants will keep upright position until 4 hours after study drug administration. Study drug will be administered 30 minutes after breakfast in the morning. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Participants' safety will be monitored throughout the study.

Registry

clinicaltrials.gov

Start Date

September 2008

End Date

October 2008

Last Updated

12 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Deemed healthy on the basis of pre-study physical examination, medical history, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory parameters performed within 2 and 21 days before first study drug administration
•Received a thorough explanation of the optional pharmacogenomic research component of the study and was offered an opportunity to participate by signing the separate pharmacogenomic informed consent document
•Female participants must be postmenopausal (at least 12 months since last menses), surgically sterile, or, if of childbearing potential or sexually active, be practicing an effective method of birth control before entry and throughout the study
•Female participants must have a negative serum beta-human chorionic gonadotropin (b-hCG) pregnancy test at Screening
•Body mass index between 20 and 28 kilogram per square meter (kg/m\^2), inclusive, and body weight not less than 50 kilogram

Exclusion Criteria

•Participants with history of seizure disorder or epilepsy mild or moderate traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm within 1 year of Screening, or severe traumatic brain injury
•History of gastrointestinal disease affecting absorption, gastric surgery or history of or current significant medical illness including cardiac arrhythmias (uneven heart beat) or other cardiac disease, hematologic disease, coagulation disorders lipid abnormalities, significant pulmonary disease,diabetes mellitus, renal or hepatic insufficiency, thyroid disease, neurologic or psychiatric (mental disorders) disease, infection, or any other illness that the investigator considers should exclude the participant - History of clinically significant allergies, especially known hypersensitivity or intolerance or contraindications to opioids, opioid antagonists, benzodiazepines, any study drug formulation component, any of the excipients of the formulation, or heparin
•History of, or a reason to believe a participant has a history of lifetime opioid abuse or, drug or alcohol abuse within the past 5 years
•Positive test for drugs of abuse, such as cannabinoids, alcohol, opiates, cocaine, amphetamines, benzodiazepines, or barbiturates at Screening or on Day -1 of the first treatment period

Arms & Interventions

Tapentadol

Tapentadol tamper resistant prolonged-release formulation (TRF) will be administered as 250 milligram oral tablet once (in the morning, 30 minutes after breakfast) on Day 1 and 6, and twice daily (in the morning, 30 minutes after breakfast and in the evening) on Day 4 and 5.

Intervention: Tapentadol

Outcomes

Primary Outcomes

Maximum Serum Concentration (Cmax) of Tapentadol

Time Frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose of tapentadol on Day 1 and 6, and pre-dose, 4, 12, 16, 24, 28, 36, 40 hours post multiple-dose administration of tapentadol on Day 4

The Cmax is the maximum plasma concentration.

Time to Reach Maximum Concentration (tmax) of Tapentadol

The tmax is time to reach the maximum observed serum concentration.

Area Under the Serum Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Tapentadol

The AUC (0-last) is the area under the serum concentration-time curve from time zero to last quantifiable time.

Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of Tapentadol

The AUC (0-infinity) is the area under the serum concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the serum concentration-time curve from time zero to last quantifiable time; C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.

Percentage of AUC (0-infinity) Obtained by Extrapolation

Percentage of AUC (0-infinity) will be obtained by extrapolation and calculated as: difference between AUC (0-infinity) and AUC (0-last)/AUC (0-infinity) multiplied by 100.

Elimination Half-Life (t [1/2] Lambda) of Tapentadol

Elimination half-life (t \[1/2\] Lambda) is associated with the terminal slope (lambda \[z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).

Rate Constant (Lambda[z])

Lambda(z) is first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve .

Time (t [last])to Reach Last Quantifiable Serum Concentration

The t (last) is the time to last quantifiable serum concentration.

Maximum Steady-State Serum Concentration (Cmax,ss) of Tapentadol

The Cmax,ss is the observed maximum serum concentration during a dosing interval at steady-state (time at which serum concentration does not change with time).

Trough Serum Concentration (C trough)

The C trough is the trough serum concentration before each dose of the multiple-dose treatment.

Time to Reach Maximum Steady-State Serum Concentration (Tmax,ss) of Tapentadol

The Tmax,ss is the time to reach the maximum serum concentration after the fifth dose of the multiple-dose treatment.

Area Under the Serum Concentration-Time Curve From Time Zero to tau (AUC [0-tau]) of Tapentadol

The AUC (0-tau) is the area under the serum concentration-time curve during a dosing interval (tau).

Steady-State Average Serum Concentration (Cavg,ss) of Tapentadol

The Cavg,ss is the average serum concentration at steady-state, calculated as AUC (tau) divided by tau.

Fluctuation Index (FI)

The FI is percentage fluctuation that is, variation between peak and trough at steady-state, calculated as difference between Cmax and Ctrough divided by Cavg,ss and multiplied by 100.

Accumulation Ratio

Accumulation Ratio calculated for AUC as AUC (x, ss) divided by AUC (x, sd) and for Cmax as C(max,ss) divided by C(max,sd).