| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Primary osteoarthritis of the hand. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10058192 |
|
| 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 |
To compare the efficacy of DSG 1%, applied four times a day vs. placebo in OA of the hand, based on assessment of three efficacy outcomes, each assessed on a 100 mm VAS, at Week 4 and Week 6:
- OA pain intensity in the dominant (target) hand over the last 24 hours.
- Total AUSCAN (Australian/Canadian) Osteoarthritis Hand Index score for the dominant hand.
- Patient global rating of disease activity. |
|
| E.2.2 | Secondary objectives of the trial |
1. Onset of efficacy of DSG in the dominant hand by assessment of above efficacy outcomes at the study site during the visits at Weeks 1 and 2, and by assessment of daily OA pain intensity in the diary over Days 1-14.
2. Durability of efficacy of DSG in the dominant hand by assessment of above efficacy outcomes at the study site during the visits at Week 8.
3. Effect of DSG in the non-dominant hand by assessment of OA pain intensity as well as the pain and function subscales of the AUSCAN index at the study site during all visits.
4. Safety and tolerability profile of DSG vs. placebo over 8 weeks. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
At Screening:
The patient must:
1. Understand the procedures, agree to participate, and give written informed consent prior to initiation of any study procedure.
2. Be able to indicate right- or left-handedness. The dominant hand will be the target hand for the primary efficacy analysis. Both right and left-handed subjects are included.
3. Have a diagnosis of primary hand OA according to ACR criteria with symptoms including pain for at least 12 months (see Post-text supplement 1),
- with a least two painful episodes in at least one finger joint during this period,
- reporting use of a NSAID or salicylate whether oral or topical, during at least one of these episodes, and
- reporting pain on > 15 days during the preceding 30 day period.
4. Report that pain is usually greater in the dominant hand.
5. Expect to need to treat the target hand for at least 7 weeks.
6. Be ≥ 40 years of age.
7. Females must be
- surgically sterilized (tubal ligation or hysterectomy), or post-menopausal for at least 12 months past last natural menses or FSH ≥20 IU/L and serum estradiol ≤18 pg/mL, or
- practicing an acceptable form of birth control for greater than 2 months prior to screening visit (defined as the use of an IUD, a barrier method with spermicide, condoms, subdermal implants or oral contraceptives). Females of child bearing potential must continue to practice their birth control during the trial.
8. Be fluent in the language in which each questionnaire is presented at the site.
9. Be able to comply with the assessment requirements, and to report AEs, intake of rescue medication and concomitant medication for the duration of the study.
At Baseline:
The patient must:
1. Rate pain in the target hand during previous 24 hours ≥ 40 mm on a 100 mm VAS.
2. If washed out from NSAIDs between screening and baseline visit, show an increase of pain over the past 24 hours in the target hand of ≥ 15 mm (on a 100 mm VAS) between the screening and the baseline visit.
3. If there is pain in the non-dominant hand, the rating of pain over the past 24 hours must be at least 20 mm lower (on a 100 mm VAS) than the corresponding rating in the target hand.
4. Have a posterior-anterior X-ray of the dominant hand, no more than one year old, showing signs of OA in the same painful joints with Kellgren-Lawrence grade 1, 2, or 3 disease in the dominant hand (Kellgren and Lawrence 1957). The specific use of the Kellgren-Lawrence grading for hand OA is detailed in Post-text supplement 2 (Hart and Spector 2000).
5. Females of childbearing potential must have a negative pregnancy test.
6. Confirm willingness to avoid the use of other topical or systemic (Rx or OTC) analgesic or anti-inflammatory treatments other than the study medications during the course of the study, including other topical anti-arthritic medications such as capsaicin or salicylate. |
|
| E.4 | Principal exclusion criteria |
1. Secondary post-traumatic OA, history and/or evidence of any other rheumatic disease involving the potential target hand or the arm: algodystrophy, septic arthritis, inflammatory joint disease (e.g. psoriatic arthritis), rapidly destructive osteoarthropathy, chondrocalcinosis, gout, recurrent episodes of pseudogout, Paget’s disease of bone, articular fracture, ochronosis, acromegaly, hemochromatosis, primary osteochondromatosis, heritable disorders , collagen gene mutations, carpal tunnel syndrome, Dupuytren’s disease and neurological diseases of the hand or arm.
2. Symptomatic OA at additional locations besides the hand(s), requiring any symptomatic or disease-modifying treatment at present or patient anticipates to require such treatment.
3. Radiological signs of OA Kellgren-Lawrence grade 4 disease in the dominant hand.
4. Adult juvenile chronic arthritis.
5. History of rheumatoid arthritis or laboratory values indicative of rheumatoid arthritis with subsequent diagnosis by a physician.
6. History of other inflammatory diseases such as colitis within the previous year.
7. History of fibromyalgia within the previous year.
8. Laboratory values with clinically significant abnormalities. Patients with elevated ESR or CRP are excluded only if clinical signs indicate an underlying clinically significant disease and in particular if both parameters are elevated.
9. Females who are pregnant or lactating.
10. Evidence of active peptic ulceration within the previous 12 months or history of GI bleeds.
11. Evidence of liver disease and/or evidence of alcohol or drug abuse.
12. Known hypersensitivity to analgesics, antipyretics, NSAIDs or any ingredients in the study medication, e.g. isopropyl alcohol or propylene glycol.
13. Not able to tolerate rescue medication with paracetamol.
14. Skin lesions or wounds in the area to be treated with the study medication on either the dominant or the non-dominant hand.
15. History of malignancy of any organ system, treated or untreated, within the past five years whether or not evidence of local recurrence or metastases exists, with the exception of localized basal cell carcinoma of the skin.
16. Significant medical problems, including but not limited to the following: uncontrolled hypertension, heart failure, type I diabetes (well controlled type II diabetes is allowed even when requiring insulin), thyroid disease (unless the patient is controlled for at least 3 months, with or without thyroid hormone substitution), known HIV seropositivity.
17. History of noncompliance to medical regimens or considered unreliable.
18. Use of medications prohibited before or during the study.
19. Use of any of the physical therapies listed among Concomitant therapies that are not allowed during the study.
20. Expects to introduce, discontinue, or change physical therapy during the study, or initiate a new exercise regime or increase the rigor of the current exercise regime. Current physical therapy must have been started at least 3 months before screening.
21. Failure to indicate a dominant hand, i.e. truly ambidextrous. Must indicate same hand used preferentially for all activities described in Questions 10-14 of the AUSCAN physical function index.
22. Inability to apply the gel correctly to either hand. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
At 4 and 6 weeks of treatment (DSG 1% vs. placebo, all based on evaluations on a 100 mm VAS):
1. OA pain intensity in the target hand (in the previous 24 hours).
2. Global rating of disease activity.
3. Total AUSCAN score in the target hand (unweighted sum of the scores on 15 questions). |
|
| 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 | Yes |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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
|
Enrollment will stop when the overall target number of patients is reached. The planned termination for this trial will be week 8 for all 360 patients (180 per group). On completion of the study, the 'Final Visit' page of the CRF will be completed.
Premature termination of the study must be mutually agreed upon by the Lead Investigator and Novartis and must be documented. However, study results will be reported according to the requirements outlined in the protocol as far as it is applicable. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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