Phase 1 Pharmacokinetic Study of Tapentadol Prolonged-Release 250 Milligram (mg) Formulation in Healthy Participants

NCT01877226 | Completed Phase 1

• 2 other identifiers: CR015466R331333PAI1036
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

Healthy; Tapentadol

Outcome Measures

Primary Outcomes (15)

• Maximum Serum Concentration (Cmax) of Tapentadol

  The Cmax is the maximum plasma concentration.

  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

• Time to Reach Maximum Concentration (tmax) of Tapentadol

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

  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

• 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.

  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

• 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.

  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

• 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.

  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

• 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).

  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

• 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 .

  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

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

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

  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

• 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).

  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

• Trough Serum Concentration (C trough)

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

  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

• 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.

  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

• 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).

  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

• 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.

  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

• 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.

  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

• 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).

  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

Study Arms (1)

Tapentadol

EXPERIMENTAL

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.

Drug: Tapentadol

Interventions

Tapentadol DRUG

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.

Tapentadol

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead

Study Sites (1)

Unknown Facility

Utrecht, Netherlands

Location

Related Links

• An open-Label, Sequential Treatment Study to Assess the Single- and Multiple-Dose Pharmacokinetics of a new Tapentadol Extended -Release 25-milligram Formulation in Healthy Subjects

MeSH Terms

Interventions

Tapentadol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 13, 2013
• Study Start: September 1, 2008
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: June 13, 2013

Record last verified: 2013-06

Locations

NL (1)