An Open-Labeled Randomized Prospective Multi-center Study to Evaluate the Efficacy and Safety of Intra-articular Injection of OSSINEXT™, an Autologous Growth Factor Concentrate (AGFC) Compared to Hyaluronic Acid (HA) in Knee Osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is known as degenerative arthritis and is the second most common rheumatologic problem with a prevalence of 22%-39% in India. Knee OA (KOA) is a major cause of mobility impairment, particularly among females. Non-surgical treatment options for KOA include intra-articular injections of platelet-rich plasma (PRP) and hyaluronic acid (HA). Most commercially available PRP preparation kits do not remove RBCs and WBCs which are detrimental to the healing effects. Wockhardt Regenerative Pvt. Ltd., Mumbai, India has developed a kit known as Ossinext™ which has an advantage over traditional PRP in that it eliminates RBCs and WBCs. This study was conducted to evaluate the effectiveness and safety of intra-articular injection of Wockhardt's Ossinext™ an autologous growth factor concentrate (AGFC) versus HA in KOA. METHODS:  Male and female patients in the age group between 30 and 75 years with confirmed KOA on radiological assessment with Grades I-III on the Kellgren-Lawrence Grading Scale and with visual analog scale (VAS) pain score of 4 or more (on the numeric rating scale) in spite of taking non-steroidal anti-inflammatory drugs (NSAIDs) since past 2 weeks were considered for study participation. This was an open-labeled study and eligible patients were randomly allocated to AGFC or HA in a 1:1 fashion. Three intra-articular injections were given in the affected knee joint, i.e. at baseline, month 1, and month 2 visits. Patients were evaluated at regular intervals, i.e. at months 5, 8, and 11 for primary and secondary endpoints. The primary efficacy endpoint for this study was change from baseline in WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) scores at month 11 whereas the secondary efficacy endpoints were change from baseline of VAS pain scale at months 1, 2, 5, 8, and 11 as well as change from baseline of WOMAC, KOOS (Knee and Osteoarthritis Outcome System), and IKDC (International Knee Documentation Committee) scale at month 5, 8, and 11. For analysis a mixed model for repeated measures was used. RESULTS:  Out of the 100 patients who were enrolled, 50 patients each were randomized to AGFC and HA arm. The results were analyzed from 99 patients (49 for AGFC and 50 for HA) who met the criteria for the modified intent to treat (mITT) population. At month 11 on the WOMAC scale, there was greater improvement seen with Ossinext™ compared to HA group which was also statistically significant with p-value of 0.0332. Within the group, there was statistically significant improvement before and after treatment in all scales, i.e. WOMAC, KOOS, IKDC, and VAS at all time points, i.e. months 5, 8, and 11 with a p-value as low as <0.0001. Within the group, the VAS score showed statistically significant improvement even at months 1 and 2 as well. A total of 24 patients reported 37 adverse events (AEs) during the study, most common being pain, pyrexia and swelling but none of the AEs reported during the study were considered as severe in intensity. There were no safety concerns reported. CONCLUSIONS: In conclusion, greater and statistically significant improvement was seen with Ossinext™ in WOMAC scores at month 11 compared to HA. Ossinext™ also showed marked statistically significant improvement from before treatment to after treatment in the WOMAC, KOOS, IKDC, and VAS scales used for the assessment of KOA with a p-value as low as <0.0001. Ossinext™ was also safe and well-tolerated.

A Prospective Multicenter Study to Evaluate the Safety and Efficacy of the Topical Application of MYOWNN™, an Autologous Growth Factor Concentrate (AGFC) Serum, in Anti-Aging.

Background Growth factors from platelets have been emerging as a revolutionary treatment with the ability to induce cell growth in the skin, which results in retarding and reversing the aging process. Platelet-rich plasma (PRP) allows for greater release of growth factors and biologically active proteins, which in turn activates the cascade of stimulation of neoangiogenesis and collagen production. PRP is used in anti-aging and facial skin rejuvenation in the form of dermal injections and topical application during micro-needling. This study was conducted to assess the safety and efficacy of a topically applied face serum, MYOWNN™ (Wockhardt Ltd., Mumbai, India). MYOWNN™ is an autologous growth factor concentrate that has been made into a topical face serum. Methods Male and female subjects in the age group between 30 and 55 years (both inclusive) with Fitzpatrick skin type III-V who had not taken any oral or topical treatments for at least four weeks before and any platelet-rich plasma (PRP) based facial treatment (injections) at least six months before the study entry were included. MYOWNN™ serum was applied on the face once daily at night, approximately 30 minutes before sleeping preferably, for a total duration of five months. Six parameters, i.e. spots, pores, wrinkles, texture, moisture, and pigmentation, were evaluated at regular intervals with Visage-LS (dermaindia®, Tamil Nadu, India), a face analysis system that gives the live status of these six parameters and is an advanced live status skin detection equipment together with shooting, analyzing, and displaying functions, as well as the subjective analysis, was performed by subjects and physicians using different globally accepted scales like physician's global aesthetic improvement scale (PGAIS), subject's global aesthetic improvement scale (SGAIS), subject satisfaction score (SSS), and wrinkle severity rating scale (WSRS). For analysis, a mixed model for repeated measures was used. The model had change from baseline as the dependent variable visit as a factor and baseline assessment result as a covariate. All primary and secondary efficacy endpoints were analyzed using Modified Intent-to-Treat (mITT) populations. Results Improvement in an average of six anti-aging parameters was observed as early as three months while statistically significant improvement was observed by the end of five months of application. A statistically significant improvement in wrinkles was observed by the end of three months of the application itself. There were no product-related adverse events reported. Conclusions Five months of application of MYOWNN™ serum showed a statistically significant improvement in an average of six parameters of anti-aging and face rejuvenation with a p-value of 0.0150 (<5% level of significance (i.e. 0.05) and was also well-tolerated.

Single-Center Investigation of the Pharmacokinetics of WCK 4282 (Cefepime-Tazobactam Combination) in Renal Impairment.

WCK 4282 is a combination product of cefepime (FEP) and tazobactam (TAZ) in a 1:1 ratio currently under development for the treatment of multidrug-resistant Gram-negative bacterial infections. We investigated the effect of renal impairment on the pharmacokinetics (PK) and safety of WCK 4282 in 48 subjects with various degrees of renal function. Subjects were categorized on the basis of their Cockcroft-Gault equation-estimated creatinine clearance (CLCR). We enrolled 6 subjects each into those with mild (CLCR, 60 to <90 ml/min), moderate (CLCR, 30 to <60 ml/min), or severe (CLCR, <30 ml/min) renal impairment and those with end-stage renal disease (ESRD) requiring hemodialysis and 24 healthy control subjects (CLCR, ≥90 ml/min). Healthy subjects and subjects with mild and moderate renal impairment received a single 90-min infusion of 4 g of WCK 4282 (2 g FEP and 2 g TAZ). Subjects with severe renal impairment and ESRD received 2 g of WCK 4282 (1 g FEP and 1 g TAZ) over 90 min. The plasma exposure of FEP-TAZ increased as renal function decreased. In subjects with mild, moderate, and severe renal impairment and ESRD, the mean exposure (area under the plasma concentration versus time curve from time zero extrapolated to infinity) of FEP and TAZ increased by 1.3- and 1.2-fold, 2.3- and 2.3-fold, 4.7- and 4.0-fold, and 8.5- and 11.6-fold, respectively. The urinary recovery of FEP and TAZ decreased with increasing renal impairment. There were no adverse events reported during the study. The findings suggest that dose adjustments for WCK 4282 will be required according to the degree of renal impairment. A single infusion of WCK 4282 was found to be safe and well tolerated in subjects with normal and impaired renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT02709382.).

Single-Center Evaluation of the Pharmacokinetics of WCK 5222 (Cefepime-Zidebactam Combination) in Subjects with Renal Impairment.

WCK 5222 is a novel ß-lactam-ß-lactam-enhancer combination of cefepime (FEP) and zidebactam (ZID). ZID is a novel ß-lactam enhancer with a dual action of binding to Gram-negative penicillin-binding protein 2 (PBP2) and ß-lactamase inhibition. WCK 5222 is being developed as a new therapeutic option for the treatment of complicated multidrug-resistant Gram-negative pathogen infections. We investigated the effect of renal impairment on the pharmacokinetics (PK) and safety of WCK 5222 in 48 subjects based on Cockcroft-Gault-estimated creatinine clearance (CLCR). We enrolled mild (n = 6; CLCR, 60 to <90 ml/min), moderate (n = 6; CLCR, 30 to <60 ml/min), and severe (n = 6; CLCR, <30 ml/min; not on dialysis) impairment, end-stage renal disease (ESRD) on hemodialysis (HD) (n = 6), and matched normal controls (n = 24; CLCR, ≥90 ml/min). Healthy control subjects and mild and moderate renal impairment subjects received a single 60-min intravenous (i.v.) infusion of 3 g WCK 5222 (2 g FEP/1 g ZID); severe renal impairment and HD subjects received a single 60-min i.v. infusion of 1.5 g WCK 5222 (1 g FEP plus 0.5 g ZID). Body and renal clearance decreased, and plasma half-life (t1/2) and the area under the concentration-time curve from time zero extrapolated to infinity (AUC0-∞ [h µg/ml]) increased in a graded relationship with severity of renal impairment for both FEP and ZID. Our findings suggest that dose adjustments for WCK 5222 will be required according to the degree of renal impairment. Overall, WCK 5222 (FEP-ZID) was found to be safe and well tolerated in subjects with normal and impaired renal function. (This study has been registered at ClinicalTrials.gov under identifier NCT02942810.).

Comparative evaluation of pharmacokinetics and pharmacodynamics of insulin glargine (Glaritus®) and Lantus® in healthy subjects: a double-blind, randomized clamp study.

AIMS: The objective of the study was to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties of an insulin glargine formulation, Glaritus® (test) with the innovator's formulation Lantus® (reference) using the euglycemic clamp technique in a single-dose, double-blind, randomized, two sequences, four-period replicate crossover study in healthy volunteers (n = 40). METHODS: Subjects received subcutaneous administration of the insulin glargine (0.4 IU/kg) formulation at two occasions for test and reference and a 20% glucose solution was infused at variable rate to maintain euglycemia for 24 h. RESULTS: Both PK [area under the plasma concentration time curve (AUC0-24 h) and maximum insulin concentration (Cmax)] and PD endpoints [area under glucose infusion rate time curve (AUCGIR0-24) and maximum glucose infusion rate (GIRmax)] demonstrated bioequivalence of Glaritus to Lantus with the 90% confidence interval of geometric mean ratio of test to reference entirely contained within 0.80-1.25. Both formulations showed equivalent geometric least-square mean LSM value (0.08 nmol/L) for Cmax. The geometric LSM AUC0-24 h value for Glaritus® (1.09 h nmol/L) was comparable to Lantus (1.05 h nmol/L). Median Tmax values were also identical (12 h for both), and median t1/2 values were also equal (18 h for both). For GIRTmax, the difference between the means for the two was not statistically significant. No AEs related to study formulations were reported, and both products were well tolerated. CONCLUSIONS: The test product (Glaritus) was found to be bioequivalent to the reference product (Lantus). CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2015/06/005890; http://www.ctri.nic.in/ .