| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| No medical condition to be investigated. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Not applicable (Chronic Pain) |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10049475 |
| E.1.2 | Term | Chronic pain |
| E.1.2 | System Organ Class | 100000004867 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The primary objective of the trial is to assess the pharmacokinetics and relative bioavailability of tapentadol following administration of 3 prototype tapentadol PR granule formulations (test formulations) each containing 25 mg tapentadol, compared to 1 tablet of Palexia® PR 25 mg (reference formulation) under fasted and fed conditions.
The main pharmacokinetic target parameters are Cmax and AUC0-t for tapentadol. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives are to assess the safety, tolerability, and palatability of the tapentadol PR granule formulations. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects have given written informed consent to participate.
2. White, male, and aged 18 years to 55 years, inclusive.
3. Body mass index between 18.5 kg/m2 and 30.0 kg/m2, inclusive, with a lower body weight limit of 50.0 kg.
4. In good health as determined by medical history (including surgical history), physical examination, 12-lead ECG, vital signs, and safety laboratory parameters. |
|
| E.4 | Principal exclusion criteria |
Exclusion criteria (Enrollment Visit for Part 1 and Part 2)
1. Resting pulse rate is less than 50 beats or equal and greater than 90 beats per minute after 5 minutes rest in a supine position.
2. Resting blood pressure after 5 minutes rest in a supine position. Systolic blood pressure is less than 110 mmHg or equal and greater than 140 mmHg. Diastolic blood pressure is less than 60 mmHg or equal and greater than 90 mmHg.
3. QT or QTcB interval prolongation of greater than 500 ms.
4 a) Any out-of-reference range value for: gamma-glutamyl transferase, serum creatinine, prothrombin time, and international normalized ratio.
b) Any exclusion range met for urinalysis and laboratory parameters: alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, glucose (fasted), lactate dehydrogenase, total protein, creatine kinase, hemoglobin, hematocrit, white blood cell count, and platelets.
c) Any out-of-reference range value for any other clinical laboratory parameter that is judged as clinically relevant by the investigator.
5. Evidence for thyroid disease.
6. History of orthostatic hypotension.
7. Positive or missing test for human immunodeficiency virus type 1/2 antibodies and antigen, hepatitis B surface antigen and core antibodies, or hepatitis C antibodies.
8. Participation in another clinical trial within the 30 days before the Enrollment Visit, or a previous IMP within a period less than 10 times its half-life, whichever is longer.
9. History of drug abuse, or alcohol abuse or has an acute intoxication with centrally acting drugs.
10. Positive or missing alcohol breath test.
11. Positive or missing drugs of abuse test.
12. History of gastric surgery, existing or suspicion of having a paralytic ileus, or current significant medical illness.
13. History of clinically significant allergies, especially known hypersensitivity/intolerance or contraindications to opioids, opioid antagonists, or any excipients of the drug formulation.
14. Any contraindication for tapentadol or drugs with mu-opioid receptor agonist activity, i.e., subjects with significant respiratory depression, and subjects with acute or severe bronchial asthma or hypercapnia.
15. History of seizure disorder, epilepsy, or mild or moderate brain injury, stroke, transient ischemic attack, brain neoplasm within 1 year of enrollment.
16. Regular use of any prescribed or non-prescribed medications within 14 days before the Enrollment Visit. Use of monoamine oxidase inhibitors within 21 days before the Enrollment Visit.
17. Not able to abstain from consuming products containing methylxanthine, alcohol, or quinine within 24 hours of the first administration of tapentadol; or Seville oranges or products containing grapefruit juice or poppy seeds within 72 hours of the first administration of tapentadol until discharge from the trial site.
18. Blood donation or acute loss of blood within 3 months before the Enrollment Visit, or intention to donate blood or blood products during the trial or within 1 month following the completion of the trial.
19. Known or suspected of not being able to comply with the requirements of the trial protocol.
20. Not able to communicate meaningfully with the investigator and staff.
21. Habitually smoking more than 10 cigarettes, 2 cigars, or 2 pipes of tobacco per day within the last 6 months before the Enrollment Visit.
22. Unable to swallow solid, oral dosage forms whole with the aid of water.
23. Employee of the investigator or trial center, as well as family members of the employees or the investigator.
Exclusion criteria (Day -1 Period 1 for Part 1 and Part 2)
24. Received IMP or an investigational device since the Enrollment Visit.
25. Any out-of-reference range value for clinical laboratory parameters or any exclusion range met for urinalysis and clinical laboratory parameters as per exclusion criterion 4.
26. Blood donation or acute loss of blood since the Enrollment Visit.
27. Regular use of any prescribed or non-prescribed medications since the Enrollment Visit.
28. Any relevant deterioration in the health of the subject that could alter the benefit/risk assessment for the subject.
29. Positive or missing alcohol breath test.
30. Positive or missing drugs of abuse test.
31. Failure to comply with trial requirements.
32. Withdrawal of informed consent.
33. Not able to communicate meaningfully with the investigator and staff.
34. Consumption of products containing methylxanthine, alcohol, or quinine 24 hours before dosing, or Seville oranges or products containing grapefruit juice or poppy seeds 72 hours before dosing.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| No endpoints have been defined for this trial. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| No endpoints have been defined for this trial. |
|
| E.5.2 | Secondary end point(s) |
| No endpoints have been defined for this trial. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| No endpoints have been defined for this trial. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
Relative Bioavailability Study.
Pediatric development program that fulfills the requirements of the Paediatric Committee (PDCO) of the European Medicines Agency. |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| Relative bioavailability study |
|
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Part 1: fasted condition, Part 2: fed condition |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| marketed tapentadol prolonged release 25 mg tablet formulation |
|
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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