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562 EFFICACY SAFETY AND TOLERABILITY OF DIACEREIN MR 100mg vs DIACEREIN 50mg IN ADULT PATIENTS WITH OSTEOARTHRITIS OF THE KNEE
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Poster Presentations / Osteoarthritis and Cartilage 18, Supplement 2 (2010) S45–S256
562 EFFICACY, SAFETY AND TOLERABILITY OF DIACEREIN MR 100mg vs DIACEREIN 50mg IN ADULT PATIENTS WITH OSTEOARTHRITIS OF THE KNEE V.P. Baliga 1 , J.D. Jagiasi 2 , M.S. Arun Kumar 3 , K. Sankaralingam 4 , V. Veerappan 5 , C.S. Bolmall 1 1 Glenmark Pharmaceuticals Ltd, Mumbai, India; 2 Sujay Hosp. and Upadhyay Nursing Home, Mumbai, India; 3 Wockhardt Hosp., Bangalore, India; 4 Zubeda Hosp., Chennai, India; 5 Pondicherry City Hosp., Pondicherry, India Purpose: A new Diacerein Modified - Release (MR) formulation has been developed in India. The present prospective, randomized, double blind, multicentric, comparative study was undertaken to evaluate efficacy, safety and tolerability of Diacerein MR 100mg and conventional Diacerein 50mg in 224 adult patients with Osteoarthritis(OA) of the Knee after approval by the respective institutional ethics committee. Methods: Patients fulfilling selection criteria were treated with Diacerein MR 100mg once daily or Diacerein 50mg twice daily for 8 weeks after obtaining their informed consent. The primary efficacy variables included Improvement in Western Ontario and McMasters (WOMAC) individual osteoarthritis (OA) indices and Composite Index (for pain, stiffness and physical function) and the Visual Analog Scale (VAS) scores (for pain) while the secondary variable included improvement in Patient’s and Physician’s Global Assessment of Arthritis. Results: Seven patients in Diacerein MR and 8 in Diacerein group were lost to follow up. Thus a total 105 patients in Diacerein MR 100mg group and 106 in Diacerein 50mg group were included in the analysis. Results indicated that there was a statistically significant(p<0.05) early reduction in the mean VAS scores, WOMAC-OA pain, stiffness and physical function scores in both the groups at the end of 8 weeks. The reduction in mean total score of WOMAC - OA was significantly (P<0.05) greater in Diacerein MR group as compared to Diacerein group at the end of the study. A greater number of patients in Diacerein MR group had good to very good effects of treatment and the difference was statistically significant (P<0.05) as per both patients and physicians global assessment as compared to Diacerein group. The incidence of diarrhea was less in Diacerein MR group compared to Diacerein group. Conclusions: Once-daily Diacerein MR 100 mg was as effective as twice daily Diacerein 50 mg but better tolerated and could be a valuable therapeutic option in patients with osteoarthritis of the knee.
563 ASSESSMENT OF THE EFFICACY, SAFETY AND TOLERABILITY OF LORNOXICAM SR 16mg Vs LORNOXICAM 8mg IN ADULT PATIENTS WITH OSTEOARTHRITIS OF THE KNEE V.P. Baliga 1 , K. Latchoumibady 2 , S. Jagtap 3 , S. Sundar 4 , H.B. Shivakumar 5 , C.S. Bolmall 1 1 Glenmark Pharmaceuticals Ltd, Mumbai, India; 2 Laxmi Ortho Clinic, Puducherry, India; 3 Grant Med. Coll. and Sir J J Group of Hosp., Mumbai, India; 4 V S Hosp., Chennai, India; 5 Ashwini Hosp., Bangalore, India Purpose: A sustained release (SR) formulation of Lornoxicam has been developed and permits once-daily dosing in the symptomatic relief of patients with osteoarthritis. The present randomized, double-blind comparative multicentric(4) study was undertaken to compare the effectiveness and tolerability of SR lornoxicam 16mg once daily and conventional lornoxicam 8mg twice daily in adult Indian patients with osteoarthritis of the knee. Methods: The present study was approved by the institutional ethics committee and patients fulfilling the selection criteria were treated with either SR lornoxicam 16mg once daily or conventional lornoxicam 8mg twice daily for eight weeks after obtaining their informed consent. The primary endpoints were Western Ontario and McMasters (WOMAC) individual osteoarthritis (OA) indices and Composite Index (for pain, stiffness and physical function) and Visual Analog Scale (VAS) scores (for pain).Safety and tolerability were assessed at the end of the study through monitoring adverse events and physical examination. Results: Of the 219 patients enrolled in the study, seven (four in the Lornoxicam SR and three in the conventional Lornoxicam group) were lost to follow-up and were considered as dropouts. Over the 8-week study period both drugs provided significant (p<0.05) sustained relief of mean pain score (WOMAC index), VAS pain score, scores of stiffness, physical
function and total WOMAC compared to baseline. However, the difference in reduction between groups was not statistically significant. Both the formulations of lornoxicam were well tolerated with a comparable number of patients 26.1% (28 of the 107) patients in the Lornoxicam SR group and 29.5%(33 of the 112) patients in the lornoxicam conventional group reporting gastrointestinal adverse events. Conclusions: The present study suggested that once daily lornoxicam SR had comparable efficacy and tolerability as conventional lornoxicam twice daily in the treatment of adult Indian patients with osteoarthritis of the knee and could therefore be a suitable therapeutic option in this group of patients by virtue of its once daily dosage regimen.
564 EFFICACY AND SAFETY OF ORAL SALMON CALCITONIN IN PATIENTS WITH KNEE OSTEOARTHRITIS: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL M. Holm-Bentzen 1 , H.C. Hoeck 2 , P. Alexandersen 3 , I. Valter 4 , T. Hala 5 , F. Radulescu 6 , B. Jendrych 7 , J.E. Badurski 8 , E. Lau 9 , M.R. John 10 , J. Loeffler 10 , M. Arnold 10 , B.J. Riis 11 , C. Christiansen 11 1 Ballerup Byvej, Ballerup, Denmark; 2 Hobrovej, Aalborg, Denmark; 3 Orla Lehmanns Gade, Vejle, Denmark; 4 J. Pärna, Tallinn, Estonia; 5 CCBR Czech AS, Pardubice, Czech Republic; 6 Aleea Buchetului, Bucharest, Romania; 7 Specjalistyczny Orodek Medycyny Wieku Dojrzaego Sp, Warszawa, Poland; 8 Centrum Osteoporozy i Chorób Kostno-Stawowych, Białystok, Poland; 9 Ctr. for Hlth.& Med. Res. CCBR Hong Kong, Queen’s Road Central, Hong Kong; 10 Novartis Pharma, Basel, Switzerland; 11 Nordic BioSci., Herlev, Denmark Purpose: Osteoarthritis (OA) is a complex disease of the joints involving subchondral bone, cartilage and synovium. Calcitonin (CT) due to its effects on cartilage and bone metabolism, might be a potential therapeutic agent for OA. As long-term administration of subcutaneous and intranasal salmon CT (sCT) is hampered by local irritation and administration difficulties, a convenient oral formulation of sCT using a 5-CNAC carrier (a molecule based on Eligen® technology from Emisphere) was developed. Oral sCT potentially treats OA by preventing or slowing articular cartilage destruction, reducing bone resorption and improving quality of subchondral bone. Primary objective: To demonstrate the superiority of oral sCT to placebo in preventing joint space narrowing of medial tibio-femoral knee joint and reducing pain and functional disability in patients with knee OA. Secondary objectives: To demonstrate effectiveness of oral sCT in the improvement of stiffness and physical activity, global improvement of the patient’s condition, prevention of knee cartilage degradation, measured by MRI, and improvement of hand OA. Exploratory objectives: Analysis of biochemical markers of cartilage and bone turnover. Safety objective: To demonstrate safety and tolerability of oral sCT for treatment of OA. Methods: In this multi-center, double-blind, placebo-controlled study, it was planned to randomize 1150 patients with knee OA (aged 51-80 years) to receive (1:1) oral sCT 0.8 mg twice daily or placebo for 24 months. Knee joint space width (JSW) is measured by X-ray at screening and after 12 and 24 months of treatment. Knee pain, function and stiffness are measured by WOMAC visual analogue scales (VAS) at screening, 1, 6, 12 and 24 months. Additional VAS assessments of pain, physical activity and global disease activity (by patient and physician). Knee cartilage volume and thickness are derived from MRI, and radiographs of hands are taken in patients with hand OA. Safety is assessed by adverse event incidence and changes in laboratory profiles and monitored by an independent Data Monitoring Committee (DMC). After interim analysis of 12 month efficacy and safety data for futility, the DMC concluded not to discontinue the study. Final analysis of all efficacy endpoints will be done after 24 months. Results: This ongoing trial has completed recruitment of 1176 patients (age 64±6.6 years, 31.6% males and 68.4% females, BMI: 29.0±4.7) randomized at 9 study sites in 6 countries till September 2008. Study results will be available in late 2010. Conclusions: This is a Phase III, randomized, placebo-controlled trial to show the efficacy and safety of oral sCT in patients with knee OA. A second study of similar design is ongoing with 1020 OA patients in 10 countries.
Poster Presentations / Osteoarthritis and Cartilage 18, Supplement 2 (2010) S45–S256
562 EFFICACY, SAFETY AND TOLERABILITY OF DIACEREIN MR 100mg vs DIACEREIN 50mg IN ADULT PATIENTS WITH OSTEOARTHRITIS OF THE KNEE V.P. Baliga 1 , J.D. Jagiasi 2 , M.S. Arun Kumar 3 , K. Sankaralingam 4 , V. Veerappan 5 , C.S. Bolmall 1 1 Glenmark Pharmaceuticals Ltd, Mumbai, India; 2 Sujay Hosp. and Upadhyay Nursing Home, Mumbai, India; 3 Wockhardt Hosp., Bangalore, India; 4 Zubeda Hosp., Chennai, India; 5 Pondicherry City Hosp., Pondicherry, India Purpose: A new Diacerein Modified - Release (MR) formulation has been developed in India. The present prospective, randomized, double blind, multicentric, comparative study was undertaken to evaluate efficacy, safety and tolerability of Diacerein MR 100mg and conventional Diacerein 50mg in 224 adult patients with Osteoarthritis(OA) of the Knee after approval by the respective institutional ethics committee. Methods: Patients fulfilling selection criteria were treated with Diacerein MR 100mg once daily or Diacerein 50mg twice daily for 8 weeks after obtaining their informed consent. The primary efficacy variables included Improvement in Western Ontario and McMasters (WOMAC) individual osteoarthritis (OA) indices and Composite Index (for pain, stiffness and physical function) and the Visual Analog Scale (VAS) scores (for pain) while the secondary variable included improvement in Patient’s and Physician’s Global Assessment of Arthritis. Results: Seven patients in Diacerein MR and 8 in Diacerein group were lost to follow up. Thus a total 105 patients in Diacerein MR 100mg group and 106 in Diacerein 50mg group were included in the analysis. Results indicated that there was a statistically significant(p<0.05) early reduction in the mean VAS scores, WOMAC-OA pain, stiffness and physical function scores in both the groups at the end of 8 weeks. The reduction in mean total score of WOMAC - OA was significantly (P<0.05) greater in Diacerein MR group as compared to Diacerein group at the end of the study. A greater number of patients in Diacerein MR group had good to very good effects of treatment and the difference was statistically significant (P<0.05) as per both patients and physicians global assessment as compared to Diacerein group. The incidence of diarrhea was less in Diacerein MR group compared to Diacerein group. Conclusions: Once-daily Diacerein MR 100 mg was as effective as twice daily Diacerein 50 mg but better tolerated and could be a valuable therapeutic option in patients with osteoarthritis of the knee.
563 ASSESSMENT OF THE EFFICACY, SAFETY AND TOLERABILITY OF LORNOXICAM SR 16mg Vs LORNOXICAM 8mg IN ADULT PATIENTS WITH OSTEOARTHRITIS OF THE KNEE V.P. Baliga 1 , K. Latchoumibady 2 , S. Jagtap 3 , S. Sundar 4 , H.B. Shivakumar 5 , C.S. Bolmall 1 1 Glenmark Pharmaceuticals Ltd, Mumbai, India; 2 Laxmi Ortho Clinic, Puducherry, India; 3 Grant Med. Coll. and Sir J J Group of Hosp., Mumbai, India; 4 V S Hosp., Chennai, India; 5 Ashwini Hosp., Bangalore, India Purpose: A sustained release (SR) formulation of Lornoxicam has been developed and permits once-daily dosing in the symptomatic relief of patients with osteoarthritis. The present randomized, double-blind comparative multicentric(4) study was undertaken to compare the effectiveness and tolerability of SR lornoxicam 16mg once daily and conventional lornoxicam 8mg twice daily in adult Indian patients with osteoarthritis of the knee. Methods: The present study was approved by the institutional ethics committee and patients fulfilling the selection criteria were treated with either SR lornoxicam 16mg once daily or conventional lornoxicam 8mg twice daily for eight weeks after obtaining their informed consent. The primary endpoints were Western Ontario and McMasters (WOMAC) individual osteoarthritis (OA) indices and Composite Index (for pain, stiffness and physical function) and Visual Analog Scale (VAS) scores (for pain).Safety and tolerability were assessed at the end of the study through monitoring adverse events and physical examination. Results: Of the 219 patients enrolled in the study, seven (four in the Lornoxicam SR and three in the conventional Lornoxicam group) were lost to follow-up and were considered as dropouts. Over the 8-week study period both drugs provided significant (p<0.05) sustained relief of mean pain score (WOMAC index), VAS pain score, scores of stiffness, physical
function and total WOMAC compared to baseline. However, the difference in reduction between groups was not statistically significant. Both the formulations of lornoxicam were well tolerated with a comparable number of patients 26.1% (28 of the 107) patients in the Lornoxicam SR group and 29.5%(33 of the 112) patients in the lornoxicam conventional group reporting gastrointestinal adverse events. Conclusions: The present study suggested that once daily lornoxicam SR had comparable efficacy and tolerability as conventional lornoxicam twice daily in the treatment of adult Indian patients with osteoarthritis of the knee and could therefore be a suitable therapeutic option in this group of patients by virtue of its once daily dosage regimen.
564 EFFICACY AND SAFETY OF ORAL SALMON CALCITONIN IN PATIENTS WITH KNEE OSTEOARTHRITIS: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL M. Holm-Bentzen 1 , H.C. Hoeck 2 , P. Alexandersen 3 , I. Valter 4 , T. Hala 5 , F. Radulescu 6 , B. Jendrych 7 , J.E. Badurski 8 , E. Lau 9 , M.R. John 10 , J. Loeffler 10 , M. Arnold 10 , B.J. Riis 11 , C. Christiansen 11 1 Ballerup Byvej, Ballerup, Denmark; 2 Hobrovej, Aalborg, Denmark; 3 Orla Lehmanns Gade, Vejle, Denmark; 4 J. Pärna, Tallinn, Estonia; 5 CCBR Czech AS, Pardubice, Czech Republic; 6 Aleea Buchetului, Bucharest, Romania; 7 Specjalistyczny Orodek Medycyny Wieku Dojrzaego Sp, Warszawa, Poland; 8 Centrum Osteoporozy i Chorób Kostno-Stawowych, Białystok, Poland; 9 Ctr. for Hlth.& Med. Res. CCBR Hong Kong, Queen’s Road Central, Hong Kong; 10 Novartis Pharma, Basel, Switzerland; 11 Nordic BioSci., Herlev, Denmark Purpose: Osteoarthritis (OA) is a complex disease of the joints involving subchondral bone, cartilage and synovium. Calcitonin (CT) due to its effects on cartilage and bone metabolism, might be a potential therapeutic agent for OA. As long-term administration of subcutaneous and intranasal salmon CT (sCT) is hampered by local irritation and administration difficulties, a convenient oral formulation of sCT using a 5-CNAC carrier (a molecule based on Eligen® technology from Emisphere) was developed. Oral sCT potentially treats OA by preventing or slowing articular cartilage destruction, reducing bone resorption and improving quality of subchondral bone. Primary objective: To demonstrate the superiority of oral sCT to placebo in preventing joint space narrowing of medial tibio-femoral knee joint and reducing pain and functional disability in patients with knee OA. Secondary objectives: To demonstrate effectiveness of oral sCT in the improvement of stiffness and physical activity, global improvement of the patient’s condition, prevention of knee cartilage degradation, measured by MRI, and improvement of hand OA. Exploratory objectives: Analysis of biochemical markers of cartilage and bone turnover. Safety objective: To demonstrate safety and tolerability of oral sCT for treatment of OA. Methods: In this multi-center, double-blind, placebo-controlled study, it was planned to randomize 1150 patients with knee OA (aged 51-80 years) to receive (1:1) oral sCT 0.8 mg twice daily or placebo for 24 months. Knee joint space width (JSW) is measured by X-ray at screening and after 12 and 24 months of treatment. Knee pain, function and stiffness are measured by WOMAC visual analogue scales (VAS) at screening, 1, 6, 12 and 24 months. Additional VAS assessments of pain, physical activity and global disease activity (by patient and physician). Knee cartilage volume and thickness are derived from MRI, and radiographs of hands are taken in patients with hand OA. Safety is assessed by adverse event incidence and changes in laboratory profiles and monitored by an independent Data Monitoring Committee (DMC). After interim analysis of 12 month efficacy and safety data for futility, the DMC concluded not to discontinue the study. Final analysis of all efficacy endpoints will be done after 24 months. Results: This ongoing trial has completed recruitment of 1176 patients (age 64±6.6 years, 31.6% males and 68.4% females, BMI: 29.0±4.7) randomized at 9 study sites in 6 countries till September 2008. Study results will be available in late 2010. Conclusions: This is a Phase III, randomized, placebo-controlled trial to show the efficacy and safety of oral sCT in patients with knee OA. A second study of similar design is ongoing with 1020 OA patients in 10 countries.