| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 19.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10023476 |
| E.1.2 | Term | Knee osteoarthritis |
| E.1.2 | System Organ Class | 100000004859 |
|
| 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 |
| Evaluation of the analgesic efficacy of a once daily application of GRT7019 for 4 weeks compared to placebo. |
|
| E.2.2 | Secondary objectives of the trial |
Further characterization of the efficacy of GRT7019, oral diclofenac, lidocaine patch, and placebo.
Evaluation of the quality of life after treatment with GRT7019, oral diclofenac, lidocaine patch, and placebo.
Evaluation of the safety and tolerability of GRT7019, oral diclofenac, lidocaine patch, and placebo.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject has given written informed consent to participate.
2. Male or female subject aged 40 years to 80 years, inclusive, at the Enrollment Visit (Day -14 to Day -7).
3. Body mass index (BMI) between 20 kg/m2 and 36 kg/m2 inclusive, with a minimal body weight of 55 kg at the Enrollment Visit.
4. Diagnosis of OA of the index knee (the one under investigation) based on American College of Rheumatology (ACR) criteria and functional capacity class of I-III and pain must be present for at least 3 months before the Enrollment Visit according to prior/concomitant diseases and surgical interventions.
5. Use of medically acceptable methods of contraception and willingness to use them during the trial if the subject or the partner of the subject is a woman of childbearing potential.
6. Subject must be on stable analgesic medications for their condition with regular intake for at
least 3 months prior to the Enrollment Visit according to their prior/concomitant diseases and
surgical interventions.
7. No intake of rescue medication during the last 3 days prior to the Baseline Visit (Day 1) (to be checked at the Baseline Visit).
8. A baseline average pain intensity of equal to or above 4 and below 8 on the NRS at the Baseline Visit on Day 1 (as calculated by the electronic diary [eDiary]).
9. Subject completed at least 5 out of 6 possible morning and evening pain intensity assessments during the last 3 days prior to the Baseline Visit and including the morning of the Baseline Visit (as calculated by the eDiary). |
|
| E.4 | Principal exclusion criteria |
1. Concurrent participation in another trial, or within 30 days before the Enrollment Visit of this trial. Depending on the nature of the previous investigational medicinal product (IMP), a longer washout may be needed.
2. Evidence or history of alcohol or drug abuse including positive or missing drugs of abuse test at the Enrollment Visit.
3. Woman of childbearing potential with a positive or missing urine β-human chorionic gonadotropin (β-hCG) pregnancy test at the Enrollment Visit.
4. Past or pending litigation due to chronic pain or disability.
5. Employees of the investigator, trial site, or sponsor, with direct involvement in the proposed trial or other trials under the direction of that investigator, trial site, or sponsor, as well as family members of employee or the investigator.
6. Any clinically significant disease that in the investigator’s opinion may affect efficacy or safety assessments or may compromise the subject’s safety during trial participation, e.g., non-stabilized hypertension, significant pulmonary, gastrointestinal (GI), endocrine, metabolic, neurological, or psychiatric disorders.
7. History or presence of malignancy, with the exception of curative treated subject or subject being in remission of cancer for at least 2 years before enrollment and not requiring treatment.
8. Surgery of any joint within 3 months of the Enrollment Visit or any scheduled surgery or painful procedure during the course of the trial.
9. Clinically relevant history of hypersensitivity, allergy, or contraindications to any of the IMPs’ drug substances and excipients, or to pantoprazole or paracetamol.
10. Known hypersensitivity or allergy to lidocaine, other amide anesthetics, or diclofenac.
11. Conditions that require treatment with forbidden medication.
12. Painful conditions other than due to OA that contribute relevantly to pain and confound the assessment of self-evaluation of pain, for instance psoriatic arthritis, gout, low back pain, or significant skin conditions such as abscesses.
13. Known or suspected inability to comply with the requirements of the trial protocol or the instructions of the trial site staff.
14. Intake of opioids or cannabinoids in the last 3 months before the Enrollment Visit.
15. Known reactions of bronchospasm, asthma, rhinitis, or urticarial after the intake of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs) in the past.
16. Hematopoietic disorder of unclear genesis.
17. Persisting or repeatedly occurred peptic ulcers or hemorrhage in the past (at least 2 distinct confirmed episodes of ulceration or bleeding).
18. Gastrointestinal bleeding or perforation in anamnesis in conjunction with previous therapy with NSAIDs.
19. Cerebrovascular or other active bleeding.
20. Severe dysfunction of the liver or kidney.
21. Known heart insufficiency (New York Heart Association [NYHA] Class II-IV), ischemia of the heart, peripheral artery occlusive disease, and/or cerebrovascular disease.
22. Skin injuries or open wounds at the site of planned patch application. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint which will be compared to placebo is the change from baseline to Week 4 of the double-blind Treatment Period in the weekly average pain intensity. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current morning pain intensity on an 11-point NRS.
Change from baseline to Week 4 of the double-blind Treatment Period in the weekly current evening pain intensity on an 11-point NRS.
Assessment of responder rate (at least 30% reduction of weekly average pain intensity on an 11-point NRS from baseline to Week 4 of the double-blind Treatment Period and average daily rescue medication intake equal to or below 500 mg paracetamol during Week 4 of the double-blind Treatment Period).
Change from baseline in pain intensity on an 11-point NRS after physical exercise at the Final Visit.
Average daily rescue medication intake during Week 4 of the double-blind Treatment Period. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.6 | Pharmacokinetic | No |
| 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 | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 11 |
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