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

Overview[ - collapse ][ - ]

Purpose 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.
ConditionHealthy
InterventionDrug: Tapentadol
PhasePhase 1
SponsorJohnson & Johnson Pharmaceutical Research & Development, L.L.C.
Responsible PartyJohnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov IdentifierNCT01877226
First ReceivedJune 11, 2013
Last UpdatedJune 11, 2013
Last verifiedJune 2013

Tracking Information[ + expand ][ + ]

First Received DateJune 11, 2013
Last Updated DateJune 11, 2013
Start DateSeptember 2008
Estimated Primary Completion DateOctober 2008
Current Primary Outcome Measures
  • 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] [Designated as safety issue: No]The Cmax is the maximum plasma concentration.
  • Time to Reach Maximum Concentration (tmax) 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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]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]) [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]The t (last) is the time to last quantifiable serum concentration.
  • Maximum Steady-State Serum Concentration (Cmax,ss) 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] [Designated as safety issue: No]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) [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]The Cavg,ss is the average serum concentration at steady-state, calculated as AUC (tau) divided by tau.
  • Fluctuation Index (FI) [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] [Designated as safety issue: No]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 [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] [Designated as safety issue: No]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).
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitlePhase 1 Pharmacokinetic Study of Tapentadol Prolonged-Release 250 Milligram (mg) Formulation in Healthy Participants
Official TitleAn 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
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.
Study TypeInterventional
Study PhasePhase 1
Study DesignEndpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionHealthy
InterventionDrug: 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.
Study Arm (s)Experimental: 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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment18
Estimated Completion DateOctober 2008
Estimated Primary Completion DateOctober 2008
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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesNetherlands

Administrative Information[ + expand ][ + ]

NCT Number NCT01877226
Other Study ID NumbersCR015466
Has Data Monitoring CommitteeNo
Information Provided ByJohnson & Johnson Pharmaceutical Research & Development, L.L.C.
Study SponsorJohnson & Johnson Pharmaceutical Research & Development, L.L.C.
CollaboratorsNot Provided
Investigators Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L.C Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Verification DateJune 2013

Locations[ + expand ][ + ]

Netherlands
Utrecht, Netherlands