Comparative Bioavailability Study of a New Vitamin D3 Orodispersible Film Versus a Marketed Oral Solution in Healthy Volunteers.

BACKGROUND AND OBJECTIVE: An orally disintegrating film (ODF) formulation of vitamin D3 that dissolves rapidly in the mouth without drinking or chewing may be a worthwhile alternative to currently available drug products for therapeutic vitamin D supplementation. This study aimed to compare the bioavailability of a single dose of a vitamin D3 25000 I.U. ODF with those of a marketed oral vitamin D3 preparation in healthy subjects. METHODS: This Phase 1, randomised, parallel-group, open-label study compared the pharmacokinetics of calcifediol [25(OH)D3], the precursor of bioactive vitamin D3, after a single dose of a new vitamin D3 25,000 I.U. ODF with those of a Reference formulation (vitamin D3 25000 I.U./2.5 mL oral solution) in healthy adult subjects using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. The primary objective was bioavailability under fed conditions, defined as maximum plasma concentration (Cmax) of 25(OH)D3 and area under the concentration-time curve from time zero to time t, the last quantifiable concentration (AUC0-t). The pharmacokinetics of 25(OH)D3 were also evaluated following the ODF administration under fasting conditions. Subjects were randomised to receive a single dose of the vitamin D3 25000 I.U. ODF or the Reference oral solution under fed conditions or the vitamin D3 ODF under fasting conditions. RESULTS: Forty-eight healthy subjects were randomised and completed the study. Overall, the pharmacokinetic profile was very similar across the three treatment groups, and bioavailability did not significantly differ among treatments. Under fed conditions, mean 25(OH)D3 plasma values for Cmax were 6.68 ± 2.03 versus 6.61 ± 2.62 ng/mL for the Test versus Reference formulations. Corresponding values for AUC0-t were 2364.80 ± 1336.97 versus 2150.52 ± 1622.76 ng/mL × h. Mean Cmax was slightly lower (6.68 ± 2.03 vs 7.23 ± 1.48 ng/mL) and the time to reach peak concentration was delayed (144 h [36-312] versus 42 h (2-480]) with the ODF under fed versus fasting conditions (p = 0.0371). The point estimates and 90 % CIs of the Testfed/Referencefed ratios of the geometric means showed that the bioavailability of exogenous 25(OH)D3 was, both in rate and extent of absorption, slightly higher with the vitamin D3 ODF than the vitamin D3 oral solution under the administration conditions recommended for the vitamin D3 oral solution. Palatability and ease of use of the ODF were satisfactory. CONCLUSION: The new ODF 25000 I.U. formulation provided a valuable alternative to the marketed oral solution for therapeutic vitamin D supplementation, with a bioavailability that was slightly higher than that of the vitamin D3 oral solution administered under the same conditions. TRIAL REGISTRATION: The study was retrospectively registered with the ISRCTN Registry (Registry code: ISRCTN13208948) on 27 November 2020.

Efficacy and Safety of a Hyaluronic Acid-Containing Gauze Pad in the Treatment of Chronic Venous or Mixed-Origin Leg Ulcers: A Prospective, Multicenter, Randomized Controlled Trial.

INTRODUCTION: Hyaluronic acid (HA)-containing formulations routinely are utilized along with standard therapy to promote faster healing of chronic wounds; evidence to guide clinical decisions on the use of topical HA in the healing of vascular leg ulcers is limited. OBJECTIVE: This study compared the efficacy and safety of an HA-impregnated gauze pad with an identical gauze pad without HA in the treatment of chronic leg ulcers of vascular origin. MATERIALS AND METHODS: A prospective, multicenter, multinational, parallel-group, randomized, double-blind, clinical study was conducted between June 13, 2017, and December 31, 2018. Adults with 1 or more chronic leg ulcers of venous or mixed origin between 2 months and 4 years' duration were eligible to participate. Participants were randomized to treatment consisting of standard care (ie, ulcer cleansing, debridement/anesthesia as necessary, and optimized compression) and either application of a gauze pad containing 0.05% HA or a neutral comparator once daily for a maximum of 20 weeks. The primary efficacy endpoint was complete ulcer healing (100% reepithelialization of the wound area centrally assessed by 1 independent and experienced assessor blinded with respect to the treatment applied, as shown on digital photographs taken under standardized conditions at or before 20 weeks and confirmed 3 weeks later). Secondary efficacy endpoints included the percentage of completely healed target ulcers, residual area of target ulcer relative to baseline, the condition of the periulcerous skin, the total amount of analgesics used, the incidence of infection at the ulcer site of the target ulcer, patient adherence to treatment, time to achieve complete healing as centrally assessed, and pain intensity as measured by a visual analog scale. RESULTS: Among the 168 participants (82 in the HA gauze pad group and 86 in the neutral gauze pad group), 33 (39.8%) in the HA group experienced complete healing of the target ulcer, which was significantly higher than the neutral comparator group (15, 18.5%; P = .002). Results in the full analysis and per-protocol sets were consistent with the primary results; no significant difference was noted in outcomes when participants' wounds were stratified according to baseline ulcer size. CONCLUSIONS: HA delivered in a gauze pad formulation could be a beneficial treatment for chronic leg ulcers of venous or mixed origin.

Efficacy and Safety of a Hyaluronic Acid-Containing Cream in the Treatment of Chronic, Venous, or Mixed-Origin Leg Ulcers: A Prospective, Multicenter Randomized Controlled Trial.

INTRODUCTION: Topical applications of hyaluronic acid (HA)-containing formulations, based on the complex and vital role of HA in all stages of the wound-healing process, are routinely used with standard therapy to promote faster healing of chronic wounds. However, evidence to guide clinical decisions on the use of topical HA in the healing of vascular leg ulcers is limited. OBJECTIVE: This study compared the efficacy and safety of topical application of a hyaluronic acid cream vs a neutral comparator (identical cream without HA) in treating subjects with chronic leg ulcers of vascular origin. MATERIALS AND METHODS: This was a prospective, multicenter double-blind randomized controlled trial. One hundred sixty-eight subjects with chronic leg ulcers of venous or mixed (venous and arterial) origin were randomized to receive either topical applications of 0.2% HA cream or neutral comparator cream for a maximum of 20 weeks. The primary efficacy endpoint was complete ulcer healing (100% reepithelialization of the wound area centrally assessed at 20 weeks or before and confirmed 3 weeks later). In both groups, topical treatment was associated with standard therapy (ulcer cleansing and optimized compression). RESULTS: The proportion of subjects with centrally assessed complete healing of the target ulcer that was confirmed 3 weeks later (primary efficacy endpoint) was substantially higher in the HA cream group (31.3%) than in the neutral cream group (14.8%; P =.009). Results in the full analysis, per protocol, and as assessed by the investigator were consistent with primary results. No significant difference in treatment effect was observed when subjects were stratified according to baseline ulcer size (≤20 cm2 or >20 cm2) regardless of topical treatment. Safety and tolerability were comparable between treatments. CONCLUSIONS: Treatment of subjects with chronic leg ulcers of venous or mixed origin with HA cream is safe, well tolerated, and results in a higher rate of healing than a neutral comparator cream.