Regen-D 150 Adverse Reactions

REGEN-D 150 has low reactogenicity and is well-tolerated. Clinical trials did not show adverse reactions to the patient.
Pre-Clinical & Clinical Trial Experience: Pre-clinical toxicological studies done on rats and rabbits concluded that the rh-EGF is safe and well tolerable with no systemic observations. The study was conducted to evaluate the potential toxicity of repeated doses (75-300 μg/Kg) of recombinant human Epidermal Growth Factor applied topically to rat and New Zealand white rabbits groups. The rh-EGF was not absorbed systematically as revealed in the systemic absorption study conducted in rabbit. These has been significant increase in the DNA and collagen contents in the skin samples treated with rh-EGF. No significant changes were observed control and treated groups with respect to protein contents in the skin.
In another study with rats (Wistarfurth) and rabbits (New Zealand white) to evaluate the potential of repeated doses (75-300 μg/Kg) of rh-EGF applied topically to rats and rabbits, it was found that there was no observable antibody response in the treated groups with EGF in both rats and rabbits. The DNA content in skin sample of treated group has significantly increased in high dose in both the species on 15^th and 31^st day. The protein content in the control and treated groups did not differ significantly in both the species studied. The collagen content was significantly increased in medium and high dose groups in males and females both the species on 15^th and 31^st day.
In a multi-centre, double-blind, randomized, parallel, placebo-controlled phase 3 study to evaluate the safety and efficacy of REGEN-D 150 as a treatment for diabetic foot ulcers, there was a reduction of healing time to an average of 9 weeks compared to the controls within the cut off observation period of 15 weeks. When compared at 15 weeks, 86% healed whereas only 50% healed in the placebo groups.
A study conducted in Wistar NIN rats to study the effect(s) of rhEGF on naproxen-induced gastric ulcer, showed that treatment with 100 μg/Kg of rhEGF significantly resulted in healing of ulcer by 14 days. There was a significant increase in immunoreactivity for Cox-2 was observed, when compared to control group.
A multi-centre, randomized, double-blind phase 3, placebo-controlled study was conducted to evaluate the safety and efficacy of recombinant human epidermal growth factor (REGEN-D 150) in patients with bed sores (pressure ulcers). Topical application of REGEN-D 150 gel applied twice daily for 12 weeks was found to be safe and efficacious as it significantly accelerates the rate and number of healing compared to placebo in subjects with bed sores (pressure ulcers). On an average, it took about 40 days to heal bed sores, in contrast it took about 78 days to heal with placebo. There was one case of rash in EGF group and two cases of irritation in placebo group. Both these conditions resolved within 48 hours and the subject continued in the study. These adverse reactions are similar to that reported in previous studies. There were no serious adverse reactions reported. None of the enrolled subjects were withdrawn from study for drug related adverse reaction.
A phase 3 multicenter double-blind, randomized (1:1) parallel study was conducted at 3 centers to evaluate the efficacy and safety of REGEN-D 150 gel applied topically in patients with Grade I or II (Wagner's classification) diabetic foot ulcers and to compare the time required for complete healing of the ulcer in the test group and control group. Healing occurred in about 13 weeks for placebo-treated ulcers and 9 weeks for the rhEGF gel-treated ulcers. The percent of completely healed ulcers in the gel-treated population in week 5, week 10, and week 15 was roughly 18%, 66% and 84%, respectively. Studies on EGF in diabetic foot ulcers have documented similar results. EGF was found to be a practical treatment solution for diabetic foot ulcers. Treatment with REGEN-D 150 was not cumbersome and does not involve complicated dressing procedures.
In a study conducted by Rajesh Kesavan et al, REGEN-D 150 was compared with placebo in patients with uninfected diabetic foot ulcers. The study showed that REGEN-D 150 increased collagen content of the wound by 3.6-fold, whereas it was 2.6-fold increase in the placebo group. Collagen type 1 expression was more in REGEN-D 150 than in placebo group. The MMP-9 expression was more in the REGEN-D 150 on the 15^th day, where it was on the 30^th day in the placebo group. The study established the safety and efficacy of REGEN-D 150 in healing of DFU.
Post-marketing Experience: Post-marketing surveillance (PMS) study of REGEN-D 150 in 135 patients with diabetic foot ulcer in India was compared with phase 3 clinical trial data of REGEN-D 150 in India. Statistical analysis of study data determined that the empirical survival probability distribution, in terms of non-healing of ulcers, was lowest in the case of PMS study, better than that for phase 3; more DFU patients were healed in PMS study. Percentage of patients cured in any given week (e.g., in week 10) is above 90% in PMS study, as compared to 69% in phase 3 clinical trial; this percentage was around 18% for the placebo-control group in the phase 3 trial. The average wound healing time was significantly lower in PMS study, 4.8 weeks, while it was 9 weeks in Phase III clinical trials while the average wound healing with REGEN-D 150 was found to be 86% in this study. REGEN-D 150 has been found to results in healthy granulation and stimulate epithelization, thus leading to final wound closure. The PMS study has established the efficacy of REGEN-D 150 in faster healing of chronic non-healing diabetic foot ulcers.
A phase 4, post-marketing surveillance study of REGEN-D 150 was undertaken to study the efficacy of rhEGF in diabetic foot ulcers. Parameters evaluated included ulcer outcome; percentage of healing; duration of healing; and quality of healing and epithelization. All patients (n=54) who were enrolled for the study resulted in good clinical outcomes, i.e. ulcers had significantly improved in terms of both percentage of wound closure and quality of healing. The average time required for the healing of an ulcer in this cohort was around 5.5 weeks. An average of 83% wound closure in the cohort was documented. Moreover, the quality and epithelization were excellent.