A Phase II Randomised, Double-blind, Parallel Group, 4-week treatment, Adaptive Dose Finding, Multi-centre study evaluating the Efficacy, Safety, Tolerability and Pharmacokinetics of up to three different oral doses of AZD1386 and Placebo in patients with Osteoarthritis of the knee

• Conditions: Osteoarthritis of the knee; MedDRA version: 9.1Level: LLTClassification code 10023476Term: Knee osteoarthritis; MedDRA version: 9.1Level: LLTClassification code 10031165Term: Osteoarthritis knee

• Registration Number: EUCTR2008-007797-37-FI
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01-02
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 520

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures.

2. Patients with OA of the knee that have unsatisfactory pain relief from past or on going nsNSAIDs/COX-2s and paracetamol/acetaminophen treatment either consecutively or simultaneously at recommended doses for at least 2 weeks, or with intolerability to past or on-going nsNSAIDs/COX-2s irrespective of doses, or dosing period, as judged by the investigator. Patients that have intolerability to NSAIDs/Cox-2s must have tried acetaminophen/paracetamol for at least 2 weeks at any time with unsatisfactory pain relief.

3. WOMAC pain on walking must be =40 mm and =90 mm VAS on both enrolment V1 and randomisation V2.

4. Male, or non-pregnant females, =40 and <80 years of age.

5.Symptomatic primary OA of the knee for at least 3 months prior to V1 according to the American College of Rheumatology (ACR).

6. Patients should belong to ACR global functional status class I, II or III (and should not be limited in their ability to perform usual self care i.e. not belong to class IV).

7. One knee should be designated as the target joint. The pain in the target joint must exceed pain experienced in other joints, and/or must exceed pain experienced from any concomitant medical condition.

8. OA in the target knee should be confirmed by X-ray at any time prior to randomisation, corresponding to at least grade 2 according to Kellgren.

9. Women of child bearing potential are eligible for participation in the study if they have a negative pregnancy test at enrolment (V1) and at randomisation (V2), see Appendix D for further guidance.

10. Patients must be both willing and able to comply with and understand the study requirements

In addition, following criterion must be fulfilled for inclusion into the optional genetic research:
11. Provision of signed, written and dated informed consent for genetic research
If a patient declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this clinical study protocol, so long as they consent.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. A current diagnosis of another form of arthritis, in addition to OA (e.g. rheumatoid arthritis, gout, septic arthritis, juvenile arthritis and lupus erythematosus) or wide spread chronic pain or fibromyalgia.

2. Patients with intra-articular or intramuscular corticosteroids or intra-articular hyaluronic acid injections within 3 months prior to randomisation.

3. Oral use of corticosteroids, barbiturates, rifampicin or phenytoin within 6 weeks prior to the randomisation visit.

4. Analgesic treatment, except low dose aspirin up to 325 mg/day for cerebrovascular and cardiovascular profylaxis.

5. Concomitant use of strong and moderate CYP3A4 enzyme inhibitors, such as ketoconazole, itraconazole, clarithromycin, nefazodone, erythromycin, fluconazole, aprepitant, diltiazem, verapamil, grapefruit juice, HIV protease inhibitors.

6. Within the last month prior the enrolment visit using >4 gram/ day (Japan: >1.5 gram/ day) of paracetamol/acetaminophen.

7. Within the last month prior the enrolment visit using more than the highest recommended dose of any NSAIDs or COX-2 inhibitors.

8. History, and/or presence, of somatic disease/condition, which may interfere with the objectives of the study as judged by the investigator.

9. Malabsorption, gastrointestinal disorder or surgery leading to impaired drug absorption.

10. History of malignancy, treated or untreated, within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin.

11. Risk factors for ventricular fibrillation e.g. family history of Short QT syndrome (SQTS) or sudden cardiac death (SCD) amongst first-degree relatives.

12. QTcF interval < 350 msec or > 450 msec at enrolment.

13. A recent history (in the past 3 months) suggestive of alcohol or drug abuse or dependence, including overuse/abuse of narcotics for management of pain.

14. Enrolment laboratory value for ALT, AST >2 times the upper limit of normal range.

15. Known positive test result for human immunodeficiency virus (HIV) antibody, hepatitis B surfactant antigen (HbsAg) or hepatitis C antibody.

16. Clinically significant abnormalities in clinical chemistry, haematology or urinalysis results as judged by the investigator.

17. Breast-feeding women.

18. Positive pregnancy test.

19. Donation of plasma within the two weeks prior to the enrolment visit and/or donation of blood within the three months prior to the enrolment visit and during the study.

20. History of allergic reaction to paracetamol/acetaminophen.

21. Involvement in the planning and conduct of the study (applies to both AZ staff and the staff at the study site).

22. Participation in another clinical trial, use of any investigational drugs or procedures or use of experimental medications within 30 days prior to the enrolment visit.

23. According to the investigator the patient should not participate in the study.

In addition, the following criteria are regarded as criteria for exclusion from the genetic research:

24. Previous bone marrow or stem cell transplant.

25. Whole blood transfusion within 120 days of the date of genetic sample collection.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified