Comparative evaluation of efficacy and safety of artesunate-lumefantrine vs. artemether-lumefantrine fixed-dose combination in the treatment of uncomplicated Plasmodium falciparum malaria.

OBJECTIVE: To establish efficacy and safety of artesunate/lumefantrine fixed-dose combination (FDC) in comparison with artemether/lumefantrine FDC in treatment of uncomplicated Plasmodium falciparum malaria. METHODS: Confirmed cases of uncomplicated P. falciparum malaria were randomly assigned to receive artesunate (100 mg)/lumefantrine (480 mg) (ASLF FDC) or artemether (80 mg)/lumefantrine (480 mg) (AMLF FDC) tablets for 3 days. Patients were followed up on Day 7, 14, 21 and 28. RESULTS: Of the 158 enrolled patients, 144 completed the study. Seventy-three patients (94.8%) from the ASLF group and 71 patients (94.7%) from the AMLF group showed parasite clearance within 48 h. The mean parasite clearance time was 25.40 ± 14.82 h in the ASLF group and 24 ± 13.32 h in the AMLF group (P = 0.542). All patients showed gametocyte clearance by Day 7 and remained gametocyte free till Day 28. Sixty-five patients (84.4%) from the ASLF group and 56 patients (74.7%) from the AMLF group were afebrile within 24 h. The mean fever clearance time was 17.38 ± 12.33 h in the ASLF group and 17.2 ± 12.01 h in the AMLF group (P = 0.929). There was one early treatment failure in the AMLF group as per WHO criteria. Improvement in haemoglobin and haematocrit was comparable in both the treatment groups. In the ASLF group, of the 25 (32.47%) patients anaemic at baseline, only seven (9.09%) reported anaemia on Day 28, while in the AMLF group, of the 14 (18.67%) patients anaemic at baseline, only four (5.33%) reported anaemia on Day 28. Both study medications were well tolerated. CONCLUSION: Artesunate (100 mg)/lumefantrine (480 mg) fixed-dose combination could add one more option to currently available artemisinin combinations in treatment of uncomplicated P. falciparum malaria.

Evaluation of efficacy and tolerability of glimepiride and metformin combination: a multicentric study in patients with type-2 diabetes mellitus, uncontrolled on monotherapy with sulfonylurea or metformin.

The objectives of this study were to evaluate the efficacy and tolerability of glimepiride plus extended release metformin (MET) on glycemic control in patients with type-2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or MET. This was a prospective, open-labeled, multicentric study over 12 weeks. Patients who were diagnosed with type-2 diabetes and were uncontrolled on monotherapy with single oral hypoglycemic agents such as glimepiride or MET and characterized by glycosylated hemoglobin (HbA1c) ≥7% and ≤10% and fasting plasma glucose (FPG) ≥ 140 mg/dL were enrolled in this study. Treatment regimen was started at 1 mg of glimepiride plus 500 mg of MET once a day and was titrated to next dose level depending on the clinician's judgment, not exceeding a total daily dose of 8 mg of glimepiride and 2000 mg of MET. After 12-weektreatment, glimepiride plus MET combination showed improvement in metabolic control as assessed by changes in HbA1c, FPG, and post prandial glucose (PPG). Primary efficacy parameter, HbA1c, was significantly reduced to (7.65 ± 1.70) at the end of the treatment from the baseline value (8.35 ± 0.93) (P < 0.001). Of the patients, 65.79% showed ≥0.5% reduction in HbA1c and or HbA1c <7% at the end of the therapy. FPG and PPG were significantly reduced at the end of the therapy as compared with baseline values (P < 0.001). Moreover, the lipid profile was also improved during the treatment period. The addition of glimepiride to MET is an effective treatment for patients inadequately controlled on sulfonylurea or Met alone. A combination of glimepiride with MET achieves good glycemic control with better tolerability profile.

Evaluation of efficacy and tolerability of gliclazide and metformin combination: a multicentric study in patients with type 2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or metformin.

The objective of this study was to compare the effects of gliclazide/metformin on glycemic control in patients with Type 2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or metformin. This was a prospective, open-labeled, multicentric study over 12 weeks. Patients who were diagnosed of Type 2 diabetes and were uncontrolled on monotherapy with oral hypoglycemic agents, including gliclazide and metformin, characterized by HbA1c 7% or greater and 10% or less and fasting plasma glucose (FPG) 140 mg/dL or greater were enrolled in this study. The treatment regimen was started at 80 mg gliclazide plus 500 mg metformin once a day and was titrated to the next dose level depending on the clinician's judgment, not exceeding a total daily dose of 320 mg gliclazide and 2000 mg metformin. Changes from baseline HbA1c, FPG, and postprandial glucose were examined. After 12-weeks treatment, the gliclazide + metformin combination showed improvement in metabolic control as assessed by changes in HbA1c, FPG, and postprandial glucose. The primary efficacy parameter, HbA1c, was significantly reduced to 7.35 ± 1.10 at the end of treatment from the baseline value (8.51 ± 0.77) (P < 0.001). A total of 84.35% of patients showed a 0.5% or greater reduction in HbA1c and 37.39% of patients reported less than 7% HbA1c at the end of therapy. FPG and postprandial glucose were significantly reduced at the end of therapy as compared with baseline values (P < 0.001). Moreover, the lipid profile was also improved during the treatment period. The addition of gliclazide to metformin is an effective treatment for patients inadequately controlled on sulfonylurea or metformin alone. A combination of gliclazide with metformin achieves good glycemic control and improves lipid levels with better tolerability profile.

A randomized, comparative, multicentric evaluation of atenolol/amlodipine combination with atenolol alone in essential hypertensive patients.

As there is a strong, positive, and continuous correlation between blood pressure and risk of cardiovascular diseases; improved control of blood pressure is necessary to produce maximum reduction in clinical cardiovascular endpoints. The primary objective was to demonstrate that atenolol/amlodipine combination therapy is superior to atenolol monotherapy with respect to mean fall in systolic blood pressure and diastolic blood pressure. The secondary objective was to compare the response rate and to evaluate the tolerability of study medications. This randomized, comparative, multicentric, 12-week study consisted of screening visit followed by baseline visit 48-hours postscreening. All enrolled patients received 7-day placebo washout. Eligible patients were randomized to receive either atenolol 25 mg/amlodipine 2.5 mg or atenolol 25 mg alone. Nonresponders after 4 weeks of therapy were escalated to atenolol 50 mg/amlodipine 5 mg or atenolol 50 mg, respectively. Out of 190 enrolled patients (94: combination group; 96: monotherapy group), 174 patients (84: combination therapy, 90: monotherapy) completed the study. After 4 weeks of therapy, low-dose combination group was superior to low-dose monotherapy with respect to mean fall in SBP (P = 0.008) and DBP (P = 0.021) and response rate (P = 0.012). Also high-dose combination therapy was superior to high-dose monotherapy with respect to mean SBP (P = 0.001), DBP (P = 0.011), and response rate (P = 0.035) at the end of 12 weeks of therapy. At the end of therapy, significantly more number of patients from combination group achieved normalization of BP (SBP < 120 mmHg and DBP < 80 mmHg) (P = 0.009). Thus, once daily treatment with atenolol/amlodipine fixed-dose combination offers superior antihypertensive efficacy over atenolol monotherapy in patients with mild-to-moderate essential hypertension.

Efficacy and tolerability of a fixed-dose combination of metoprolol extended release/amlodipine in patients with mild-to-moderate hypertension: a randomized, parallel-group, multicentre comparison with losartan plus amlodipine.

BACKGROUND: Epidemiological studies and clinical trials have shown that prevention of cardiovascular disease, the ultimate goal of hypertension treatment, requires a sufficient reduction in blood pressure. OBJECTIVE: The primary objective of this study was to compare the mean decrease in systolic (SBP) and diastolic (DBP) blood pressure between metoprolol extended release (XL)/amlodipine fixed-dose combination and losartan plus amlodipine combination in patients with mild-to-moderate essential hypertension. The secondary objectives of this study were to compare the proportion of responders in the two treatment groups and to evaluate the tolerability of the study medications. METHODS: This was a randomized, parallel-group, multicentre comparative study conducted at the outpatient departments of three teaching hospitals in India. Patients with mild-to-moderate hypertension (defined as DBP 90-109 mmHg) aged between 18 and 75 years were enrolled in this study and followed up for 12 weeks. Response to study treatments was evaluated in terms of mean decrease in SBP and DBP and the response rate (reduction to SBP <140 mmHg and DBP <90 mmHg). RESULTS: Out of 152 patients who underwent a 1-week placebo washout, 148 eligible patients were randomized to receive either metoprolol XL 25 mg/amlodipine 2.5 mg fixed-dose combination (76 patients) or losartan 25 mg plus amlodipine 2.5 mg (72 patients). The two treatment groups were similar with respect to demographic and baseline characteristics. Non-responders after 4 weeks of therapy were escalated to metoprolol XL 50 mg/amlodipine 5 mg fixed-dose combination or losartan 50 mg plus amlodipine 5 mg, respectively. The study was completed by 66 patients in each group, of whom 43 patients in each group responded to the starting doses. After 4 weeks' therapy, both treatments were associated with significant decreases in SBP and DBP from baseline (p < 0.001) and were comparable with respect to mean decrease in SBP (p = 0.304), mean decrease in DBP (p = 0.630) and response rate (p = 1.0). Also, both the step-up therapies were comparable with respect to mean decrease in SBP (p = 0.484), mean decrease in DBP (p = 0.650) and response rate (p = 0.134) at week 12. Both treatments were well tolerated in the studied population. CONCLUSION: Metoprolol XL/amlodipine fixed-dose combination was found to be as effective and well tolerated as losartan plus amlodipine in the treatment of essential hypertension.

Aceclofenac-tizanidine in the treatment of acute low back pain: a double-blind, double-dummy, randomized, multicentric, comparative study against aceclofenac alone.

Tizanidine and aceclofenac individually have shown efficacy in the treatment of low back pain. The efficacy and tolerability of the combination have not yet been established. The objective of the study was to evaluate the efficacy and safety of aceclofenac-tizanidine fixed dose combination against aceclofenac alone in patients with acute low back pain. This double-blind, double-dummy, randomized, comparative, multicentric, parallel group study enrolled 197 patients of either sex in the age range of 18-70 years with acute low back pain. The patients were randomized to receive either aceclofenac (100 mg)-tizanidine (2 mg) b.i.d or aceclofenac (100 mg) alone b.i.d for 7 days. The primary efficacy outcomes were pain intensity (on movement, at rest and at night; on VAS scale) and pain relief (on a 5-point verbal rating scale). The secondary efficacy outcomes measures included functional impairment (modified Schober's test and lateral body bending test) and patient's and investigator's global efficacy assessment. aceclofenac-tizanidine was significantly superior to aceclofenac for pain intensity (on movement, at rest and at night; P < 0.05) and pain relief (P = 0.00) on days 3 and 7. There was significant increase in spinal flexion in both the groups from baseline on days 3 and 7 with significant difference in favour of the combination group (P < 0.05). There were significantly more number of patients with excellent to good response for the aceclofenac-tizanidine treatment as compared to aceclofenac alone (P = 0.00). Both the treatments were well tolerated. In this study, aceclofenac-tizanidine combination was more effective than aceclofenac alone and had a favourable safety profile in the treatment of acute low back pain.

Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring.

BACKGROUND: Thiazide and thiazide-like diuretic agents are being increasingly used at lower doses. Hydrochlorothiazide (HCTZ) in the 12.5-mg dose remains the most commonly prescribed antihypertensive agent in the United States. OBJECTIVES: This study compared chlorthalidone, 6.25 mg daily, with HCTZ, 12.5 mg daily, by 24-h ambulatory blood pressure (ABP) monitoring and evaluated efficacy. Because HCTZ has been perceived as a short-acting drug, a third comparison with an extended-release formulation (HCTZ-controlled release [CR]) was added. METHODS: This 12-week comparative, double-blind, outpatient study randomized 54 patients with stage 1 hypertension to receive either chlorthalidone, 6.25 mg, (n = 16); HCTZ 12.5 mg (n = 18); or HCTZ-CR 12.5 mg (n = 20). ABP monitoring was performed at baseline and after 4 and 12 weeks of therapy. RESULTS: All 3 treatments significantly (p < 0.01) lowered office BP at weeks 4 and 12 from baseline. At weeks 4 and 12, significant reductions in systolic and diastolic 24-h ambulatory and nighttime BP (p < 0.01) were observed with chlorthalidone but not with HCTZ. At weeks 4 (p = 0.015) and 12 (p = 0.020), nighttime systolic ABP was significantly lower in the chlorthalidone group than in the the HCTZ group. With HCTZ therapy, sustained hypertension was converted into masked hypertension. In contrast to the HCTZ group, the HCTZ-CR group also showed a significant (p < 0.01) reduction in 24-h ABP. All 3 treatments were generally safe and well tolerated. CONCLUSIONS: Treatment with low-dose chlorthalidone, 6.25 mg daily, significantly reduced mean 24-h ABP as well as daytime and nighttime BP. Due to its short duration of action, no significant 24-h ABP reduction was seen with HCTZ, 12.5 mg daily, which merely converted sustained hypertension into masked hypertension. Thus, low-dose chlorthalidone, 6.25 mg, could be used as monotherapy for treatment of essential hypertension, whereas low-dose HCTZ monotherapy is not an appropriate antihypertensive drug. (Comparative Evaluation of Safety and Efficacy of Hydrochlorothiazide CR with Hydrochlorothiazide and Chlorthalidone in Patients With Stage I Essential Hypertension; CTRI/2013/07/003793).

Sustained Release Formulation of Primaquine for Prevention of Relapse of Plasmodium vivax Malaria: A Randomized, Double-Blind, Comparative, Multicentric Study.

Background. Primaquine is used to eradicate latent Plasmodium vivax parasite from liver, with administration of standard dose daily up to 14 days. We studied efficacy, safety, and tolerability of sustained release (SR) formulation of primaquine in comparison with conventional primaquine in preventing relapse of P. vivax malaria. Methods. Microscopically confirmed cases of P. vivax malaria received chloroquine therapy for three days. Aparasitemic and asymptomatic patients were then randomized to receive either conventional primaquine 15 mg for 14 days or primaquine SR 15 mg for 14 days, or primaquine SR 30 mg for seven days. Results. Of the 360 patients, who received chloroquine therapy, 358 patients were randomized. Two-hundred eighty-eight patients completed six-month follow-up and four patients (three: conventional primaquine 15 mg (2.86%), one: primaquine SR 30 mg (0.93%)) showed relapse confirmed by PCR genotyping. Drug compliance was significantly better in primaquine SR 30 mg group (95.57%, p = 0.039) without any serious adverse events. Conclusion. Primaquine SR 15 mg and primaquine SR 30 mg could be an effective alternative to conventional primaquine 15 mg due to their comparable cure rates and safety profile. Shorter treatment duration with primaquine SR 30 mg may increase patient compliance and may further reduce relapse rates. Clinical Trial Registration. This trial is registered with CTRI/2010/091/000245.

Efficacy and safety of fixed dose combination of atorvastatin and hydroxychloroquine: a randomized, double-blind comparison with atorvastatin alone among Indian patients with dyslipidemia.

OBJECTIVE: To evaluate the efficacy and safety of atorvastatin + hydroxychloroquine fixed-dose combination tablets in comparison with atorvastatin alone in treatment of dyslipidemia. METHODS: This double-blind, randomized, out-patient study was conducted in 328 patients with primary dyslipidemia having low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL (3.37 mmol/L) to ≤ 250 mg/dL (6.48 mmol/L) and triglycerides ≤ 400 mg/dL (4.52 mmol/L). Eligible patients were randomized to receive either atorvastatin 10 mg (n = 167) or atorvastatin 10 mg + hydroxychloroquine 200 mg (n = 161) for 24 weeks. CLINICAL TRIAL REGISTRATION: CTRI/2010/091/006138. MAIN OUTCOME MEASURES: To compare percentage change in LDL-C, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to Week 12 and Week 24 between groups. To compare mean change in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), high-sensitivity C-reactive protein (Hs-CRP), and percentage of patients achieving lipid goals at Week 12 and Week 24. RESULTS: At Week 24, percentage reduction in LDL-C (-32.52 [-36.13 to -28.91] vs -39.54 [-43.25 to -35.83]; p = 0.008), TC (-24.41 [-27.10 to -21.72] vs -29.30 [-32.07 to -26.54]; p = 0.013), and non-HDL-C (-30.37 [-33.71 to -27.04] vs -36.76 [-40.18 to -33.33]; p = 0.009) was significantly greater in combination treated patients. Both the treatments showed a significant reduction in triglycerides at Week 24 from baseline, however, this reduction was not statistically significantly different between treatment groups. No significant change in HDL-C was observed in patients from both the treatment groups. At Week 24, change in HbA1c (0.22 [0.07 to 0.37] vs -0.13 [-0.28 to 0.03]; p = 0.002) and FBG was also statistically significant in favor of combination therapy (0.37 [0.07 to 0.67] vs -0.29 [-0.59 to 0.03]; p = 0.003), whereas no statistically significant difference was observed in change in Hs-CRP (p = 0.310). Significantly more patients from the combination group achieved LDL-C and TC goals. Exploratory analysis in patients with pre-diabetes showed development of diabetes in 8 patients (15.09%) from the monotherapy group and 1 patient (1.96%) from the combination group (p = 0.034). Study medications were generally safe and well tolerated. CONCLUSION: Based on study results and widely reported pleiotropic benefits, hydroxychloroquine could emerge as a potential drug for combination with statins for treatment of dyslipidemia. Long duration studies with larger sample sizes are required to further explore the role of hydroxychloroquine as adjunct to statins in reducing risk of cardiovascular events and prevention of statin-induced diabetes.

Efficacy and safety of hydroxychloroquine in the treatment of type 2 diabetes mellitus: a double blind, randomized comparison with pioglitazone.

OBJECTIVE: To compare efficacy and safety of hydroxychloroquine with pioglitazone in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This double-blind study randomized 267 uncontrolled type 2 diabetes patients (HbA1c ≥7.5% and ≤11.5%), post 3 months' treatment with glimepiride/gliclazide and metformin, to additionally receive hydroxychloroquine 400 mg/day (n = 135) or pioglitazone 15 mg/day (n = 132) for 24 weeks. Efficacy was assessed by changes in HbA1c, fasting (FBG) and post-prandial (PPG) blood glucose at Week 12 and Week 24. RESULTS: At Week 12 and Week 24, HbA1c, FBG and PPG significantly reduced from baseline in both groups. Mean reduction in glycemic parameters at Week 12 (HbA1c: -0.56% vs -0.72%, p = 0.394; FBG: -0.99 mmol/L vs -1.05 mmol/L, p = 0.878; PPG: -1.93 mmol/L vs -1.52 mmol/L, p = 0.423) and Week 24 (HbA1c: -0.87% vs -0.90%, p = 0.909; FBG: -0.79 mmol/L vs -1.02 mmol/L, p = 0.648; PPG: -1.77 mmol/L vs -1.36 mmol/L, p = 0.415) was not significantly different between the hydroxychloroquine and pioglitazone groups. Change in total cholesterol (TC) and LDL-C was significant in favor of hydroxychloroquine (TC: -0.37 mmol/L vs 0.03 mmol/L, p = 0.002; LDL-C: -0.23 mmol/L vs 0.09 mmol/L, p = 0.003). Triglycerides significantly reduced in both groups at Week 24. Mean HDL-C remained unchanged. Study treatments were well tolerated. CONCLUSION: With favorable effects on glycemic parameters and lipids, hydroxychloroquine may emerge as well tolerated therapeutic option for T2DM. LIMITATIONS: The sample size for this study was small. However, based on the encouraging results of this proof-of-concept study, longer duration studies in larger population can be conducted to further confirm these findings. TRIAL REGISTRATION DETAILS: Clinical Trial Registry-India URL: http://ctri.nic.in, Registration Number: CTRI/2009/091/001036.

Comparison of gastrointestinal safety and tolerability of aceclofenac with diclofenac: a multicenter, randomized, double-blind study in patients with knee osteoarthritis.

OBJECTIVE: To compare the gastrointestinal (GI) tolerability and efficacy of aceclofenac with diclofenac in patients with knee osteoarthritis (OA). METHODS: In this randomized, double-blind, double-dummy, multicentric, comparative study, post 7 day placebo washout, patients were randomly allocated to receive either aceclofenac 100 mg b.i.d. or diclofenac 50 mg t.i.d. and were followed up for the next 6 weeks. The GI tolerability was evaluated based on the incidence and severity of predefined GI adverse events (AEs), number of gastroprotective agents (GPAs) consumed by patients, and discontinuation from the study due to GI AEs. The secondary outcome included assessment of pain intensity using a visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC) score, pain relief score, and investigators' and patients' overall assessments of response to study drugs. RESULTS: A total of 591 (aceclofenac group: 297; diclofenac group: 294) patients were enrolled. The cumulative incidence of GI AEs for dyspepsia (28.1% versus 37.9%; p = 0.014), abdominal pain (19% versus 26.3%; p = 0.037), overall incidence of predefined GI AEs (57.3% versus 73.6%; p < 0.001) and number of patients reporting GI AEs (28.9% versus 36.5%; p = 0.053) were significantly less in the aceclofenac group compared to the diclofenac group throughout the study. All the AEs were mild to moderate in intensity. Fewer patients from the aceclofenac group required GPAs compared to the diclofenac group (28.17% versus 33.68%; p = 0.155). During first 7 days of therapy, >90% of patients from aceclofenac group did not require GPAs. There were no differences between the study groups in the various pain assessment scales when measured during the study period. CONCLUSION: Aceclofenac was better tolerated in terms of incidence and severity of GI AEs and GPA requirement and was as efficacious as diclofenac. The need for GPAs increased with the increase in duration of treatment with NSAIDs. Hence, it could be concluded that usual practice of co-prescription of GPAs with aceclofenac could be avoided to improve patient compliance and reduce cost of treatment. However, long term trials with endoscopic evaluation in the wider population are required to assess the GI tolerability of aceclofenac and diclofenac in detail.

Comparative evaluation of efficacy and safety of etodolac and diclofenac sodium injection in patients with postoperative orthopedic pain.

OBJECTIVE: The objective of this study was to compare the analgesic efficacy of etodolac injection and diclofenac injection in patients with postoperative orthopedic pain. METHODS: This was multicentric, randomized, assessor-blind and parallel-group study. A group of 158 patients with moderate to severe pain following orthopedic surgery were randomly assigned to receive either etodolac 400 mg twice a day (n = 78) or diclofenac 75 mg thrice a day (n = 80). MAIN OUTCOME MEASURES: The primary efficacy outcome measures were pain intensity difference, sum of pain intensity differences and pain relief whereas secondary efficacy variables included maximum fall in pain intensity, number of doses of study medication consumed, number of patients who required rescue medication and overall response to therapy. RESULTS: Mean pain intensity differences assessed on 10 cm VAS were significantly better for etodolac arm compared to diclofenac arm at 4, 8, 20 and 24 hours (p < 0.05). Sum of pain intensity differences over the first 8 hours (-21.31 ± 6.26 for etodolac vs. -19.13 ± 6.98 for diclofenac; p = 0.041) and over the 24 hours (-39.83 ± 10.70 for etodolac vs. -35.25 ± 12.00 for diclofenac; p = 0.012) for the etodolac group was significantly superior than diclofenac group. Assessment of pain relief showed that etodolac injection was significantly more effective than diclofenac injection (p < 0.0001) over the 24 hour assessment period. Maximum fall in pain intensity score, number of doses of study medication consumed and patients' and investigators' overall response to the drug at the end of treatment period were also significantly superior in the etodolac arm as compared to the diclofenac arm (p < 0.05). However, the number of patients who were rescued was comparable in both the treatment arms. A change in emotional functioning of the patients was not captured in this study. Both the study medications were well tolerated with no incidence of SAE throughout the study. CONCLUSION: Etodolac can be considered as an effective alternative to traditional NSAIDS in the treatment of post operative pain.

Zaltoprofen, a noninferior alternative to diclofenac for the treatment of primary knee osteoarthritis -- a comparative evaluation of efficacy and safety in a 4-week, multicentric, randomized, double-blind, double-dummy trial.

OBJECTIVE: To demonstrate the clinical noninferiority of the analgesic effect of zaltoprofen (80 mg t.i.d.) compared with diclofenac (50 mg t.i.d.) in active knee osteoarthritis patients. METHOD: In this multicentric, double-blind, double-dummy, randomized, parallel-group, comparative study, 213 patients of either sex, aged 40 - 65 years having radiological and clinically confirmed primary knee osteoarthritis were randomized either to zaltoprofen (n = 105) or diclofenac (n = 108) and were followed-up at weeks 1, 2, 3 and 4. The treatment period was preceded by a washout period of 1 week. RESULTS: Patients in both the zaltoprofen and diclofenac groups exhibited significant improvement (p < 0.001) in pain intensity, functional status and pain relief at each visit from baseline with no statistically significant difference between the two treatment groups. There was no statistically significant difference between the treatment groups for global assessment rating done by the patient and investigator at the end of therapy (p > 0.05) and the proportion of patients who consumed ranitidine (p = 0.135) and paracetamol (p = 0.086) tablets during the treatment period on both the treatment arms. Both the study medications were well tolerated with no incidence of serious adverse events. CONCLUSIONS: This study demonstrated that efficacy and safety of zaltoprofen is clinically noninferior to that of diclofenac.