Clinical trial NCT02913521: Bioequivalence Study With Clinical Endpoint for Diclofenac Sodium Topical Gel 1%
Official title: A Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Three-Arm, Multi-Site Study to Evaluate the Clinical Equivalence of Diclofenac Sodium Topical Gel 1% (Hi-Tech Pharmacal Co., Inc.) With Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% (Novartis) in Patients With Osteoarthritis of the Knee
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Osteoarthritis, Knee
Lead sponsor: Akorn, Inc.
Sponsor class: INDUSTRY
First posted: 2016-09-23
Enrollment: 934
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Double-Blind, Randomized, Placebo-Controlled, Parallel Group, Three-Arm, Multi-Site Study to Evaluate the Therapeutic Equivalence of Diclofenac Sodium Topical Gel 1% (Hi-Tech Pharmacal Co., Inc.) With Voltaren® Gel (Diclofenac Sodium Topical Gel) 1% (Novartis) in Patients With Osteoarthritis of the Knee


Eligibility criteria: Inclusion Criteria:

1. Ambulatory male and non-pregnant females 35 years and older diagnosed with osteoarthritis according to the American College of Rheumatology Criteria (ACR) in one knee. Target knee is the one with higher level of pain.

   ACR Criteria includes: Knee Pain and at least 3 of the following: age ≥ 50, stiffness lasting \< 30 mins, bony tenderness, crepitus, bony enlargement, and no palpable warmth.
2. Symptom onset of \> 6 Months prior to Screening for the target knee.
3. If female and of child-bearing potential, prepare to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g., IUD, oral, transdermal, injected, implanted hormonal contraceptives or condom + spermicide).
4. Periarticular knee pain due to osteoarthritis (not bursitis, tendonitis etc.) that required the use of oral or topical treatments (e.g., NSAIDs or acetaminophen).
5. Radiograph of the target knee within the previous year with a Grade 1, 2 or 3 disease based upon the Kellgren-Lawrence disease severity scale.
6. After a minimum of 7-day wash out of all pain medication has Baseline pain on movement score of ≥ 50mm on a 0-100-mm Visual Analogue Scale for the target knee.
7. After a minimum of 7-day wash out of all pain medication has Baseline WOMAC Pain sub scale of ≥ 9 on a 5 question, 5 point (0 to 4) Likert scale for the target knee.
8. Willing and able to use only acetaminophen as rescue medication.
9. Willing and able to comply with the study requirements.

Exclusion Criteria:

1. Females who are pregnant, breast feeding, or planning a pregnancy.
2. Radiograph of the target knee within the previous year with a Grade 4 score on the Kellgren-Lawrence disease severity scale.
3. History of osteoarthritis in the contralateral knee requiring medication (OTC or prescription) within 12 months of screening.
4. After a minimum of 7-day wash out of all pain medication has Baseline pain on movement score of ≥ 20mm on a 0-100-mm Visual Analogue Scale for the contralateral knee immediately prior to randomization.
5. Known history of secondary osteoarthritis (e.g. congenital, traumatic, gouty arthritis) of the knee or rheumatoid arthritis.
6. Known history of other chronic inflammatory diseases, (e.g., colitis) or fibromyalgia during last 5 years. Patients whose disease was diagnosed at least 5 (five) years prior to screening visit and have had no known disease activity (i.e., no disease related complaints nor disease treatment prescribed) since then may enter into the study.
7. History of asthma, hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function or liver disease. Patients who have had high blood pressure measured at least 2 (two) years prior to screening visit and have had no disease activity (i.e., no record of hypertension or anti-hypertensive treatment prescribed) for at least 2 (two) years prior to screening visit may enter into the study.
8. History of coronary artery bypass graft within 6 months of screening.
9. Concomitant acetylsalicylic acid therapy other than a stable low dose used for cardiac prophylaxis (max. 162 mg daily) taken for at least 3 months prior to enrollment and maintained throughout the duration of the study.
10. Use of warfarin or other anticoagulant therapy within 30 days of screening.
11. Use of ACE inhibitors, cyclosporine, diuretics, lithium or methotrexate, within 30 days of screening or during the study.
12. Known history of gastrointestinal bleeding or peptic ulcer disease.
13. Abnormal screening clinical laboratory evaluations which the Investigator deems clinically significant.
14. Known allergy to aspirin or NSAIDs.
15. Skin lesions or wounds in the affected area.
16. Significant (requiring surgery) injury or major knee surgery to either knee within six months prior to screening.
17. Transaminase levels that are more than two times the upper limit of the normal range at screening.
18. Any other acute or chronic illness that in the opinion of the investigator could compromise the integrity of study data or place the Patient at risk by participating in the study.
19. Concomitant use of corticosteroids (any formulation) or use within 30 days of study randomization.
20. Receipt of any drug as part of a research study within 30 days prior to screening.
21. Previous randomization into this study.
22. Known allergy (hypersensitivity) to acetaminophen.

Primary outcomes:
measure: Mean Change From Baseline to Week 8 in WOMAC Pain Scale, Bioequivalence of Test to Reference.
timeFrame: 8 weeks
Secondary outcomes:
measure: An Evaluation to Determine Superiority of Test and Reference Against Placebo in the Mean Change From Baseline to Week 8 in the Total WOMAC Pain Score.
timeFrame: 8 weeks
measure: Incidences of Treatment Emergent Adverse Events
timeFrame: 8 weeks
measure: Incidences of Abnormal Vital Signs
timeFrame: 8 weeks
measure: Clinically Significant Changes From Baseline in Physical Examination Results
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Paide
country: Estonia
facility: Vee Family Doctor's Center OY
city: Parnu
country: Estonia
facility: OU Mai Perearstid
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital
city: Tallinn
country: Estonia
facility: Medicum Ltd.
city: Tallinn
country: Estonia
facility: Linna Health Cerntre
city: Tallinn
country: Estonia
facility: Linnamoisa Perearstikeskus
city: Tallinn
country: Estonia
facility: OU Perearstikeskus Remedium
city: Tallinn
country: Estonia
facility: Pirita Family Doctors Centre
city: Tartu
country: Estonia
facility: Orthopaedic and Clinical Research Center
city: Tartu
country: Estonia
facility: Dr.Monika Vask Ltd.
city: Tartu
country: Estonia
facility: Ltd. Elli Kahar
city: Daugavpils
country: Latvia
facility: Association of Health Centres, Medical Centre "OLVI"
city: Liepaja
country: Latvia
facility: D.Saulites-Kandevicas private practice
city: Riga
country: Latvia
facility: SIS Klinika ALma
city: Riga
country: Latvia
facility: Health Center 4
city: Kaunas
country: Lithuania
facility: InMedica
city: Kaunas
country: Lithuania
facility: JSC Vita Longa
city: Kaunas
country: Lithuania
facility: JSC Saules seimos medicinos centras
city: Klaipeda
country: Lithuania
facility: JSC Mano Seimos Gydytojas
city: Vilnius
country: Lithuania
facility: Private Doctor Family Clinic JSc Ausveja
city: Warsaw
country: Poland
facility: Medical Chamber in Warsaw Nr 5718455
state: Mazovia
city: Bialystok
country: Poland
facility: CERMED
city: Bialystok
country: Poland
facility: ClinicMed Badurski i Wspolnicy Spolka Jawna
city: Bielsko-Biala
country: Poland
facility: St. Luke's hospital in Bielsko-Biala
city: Czestochowa
country: Poland
facility: Private medical practice Jacek Niski
city: Lodz
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej ORTMED sp. z o.o.
city: Lublin
country: Poland
facility: Clinical Best Solutions
city: Olawa
country: Poland
facility: ZOZ w Olawie
city: Oswiecim
country: Poland
facility: MEDICOME Sp. z o.o.
city: Poznan
country: Poland
facility: Centrum Medyczne Luxmed, Przezmierowo
city: Warsaw
country: Poland
facility: "REUMA TIKA- Centrnrn Reurnatologii" NZOZ
city: Bacau
country: Romania
facility: Spiratul Judetean de Urgenta Bacau
city: Bacau
country: Romania
facility: Spital Judetean De Urgenta Bacau
city: Bucharest
country: Romania
facility: Duo Medical
city: Bucharest
country: Romania
facility: S.C. lanuli Med Consult Str Intr Lt. Dumitru Lemnea
city: Bucharest
country: Romania
facility: Dr Ion Stoia Rheumatology Center
city: Bucharest
country: Romania
facility: Emergency County Hospital SF Gheorghe
city: Iasi
country: Romania
facility: RK Medcenter SRL
city: Marasti
country: Romania
facility: S.C. Clinica Somesan
city: Ploiesti
country: Romania
facility: Ploiești Municipal Hospital
city: Cherkasy
country: Ukraine
facility: Communal Institution "Cherkasy Regional Hospital of Cherkasy Regional Council"
city: Dnipropetrovsk
country: Ukraine
facility: State Institution "Ukrainian State Scientific and Research Institute of Medical and Social Problems of Disability of the Ministry of Health of Ukraine
city: Kharkiv
country: Ukraine
facility: State Institution "Professor M.I. Sytenko Institute of Spine and Joint Patholo of the National Academ of Medical Sciences of Ukraine
city: Kyiv
country: Ukraine
facility: Communal Institution of Kyiv Regional Council "Kyiv Regional Clinical Hospital"
city: Kyiv
country: Ukraine
facility: State Institution D.F.Chebotariov Institute of Gerontology of NAMS of Ukraine
city: Kyiv
country: Ukraine
facility: State Institution D.F.Chebotariov Institute ofGerontolo!.!v ofNAMS of Ukraine - Dept of Age related changes to Muscoskeletal system
city: Lviv
country: Ukraine
facility: Communal Institution of.Lviv Regional Council "Yu. Lypa Lviv Regional Hospital of Disabled War Veterans and Former Political Prisoners"
city: Odesa
country: Ukraine
facility: Odesa Regional Clinical Hospital
city: Vinnytsya
country: Ukraine
facility: MI Pyogrov Vinnystya Regional Clinical Hospital
Study officials:
affiliation: EGeen International Inc.
name: Kalev Kask, Ph.D.
role: STUDY_DIRECTOR
References: