Aminolevulinic acid hydrochloride 30mg/ml oral solution

OBJECTIVE: To evaluate the efficacy and safety of 5-aminolevulinic acid hydrochloride/sodium ferrous citrate (5-ALA-HCl/SFC) in patients with adult-onset Still's disease (AOSD) refractory to corticosteroids. METHODS/DESIGN: This multicenter, investigator-initiated, randomized, double-blind, placebo-controlled, parallel-group phase II trial was designed to enroll 30 participants but was prematurely terminated after enrolling four participants because of slow recruitment. Participants were randomized to receive 5-ALA-HCl/SFC (100 or 300 mg/day) or placebo for 8 weeks. The primary endpoint was the achievement of adapted ACR 30 at week 4. RESULTS: All four enrolled participants achieved adapted ACR 30 at week 4. Adapted ACR 50/ 70/ 90 responses and improvements in systemic feature score, serum ferritin, and quality of life varied among individuals. No serious adverse events were observed. CONCLUSION: Efficacy signals were observed, especially in the high-dose group; however, the small sample size precludes definitive conclusions. Further research is required to confirm this.

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Abstract Objective A phase III, double-blind, placebo-controlled, randomized withdrawal trial of SPP-004 (5-aminolevulinic acid hydrochloride and sodium ferrous citrate) in patients diagnosed as Leigh syndrome (LS) was conducted to confirm the efficacy and safety of SPP-004 in patients with LS showing central nervous system disorders. Methods Fifty-four patients entered a 24-week open-label period of SPP-004 administration. Among them, 28 patients showing improved scores on the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) for cranial nervous symptoms and myopathy symptoms proceeded to a 48-week double-blind (DB) period, where they were randomized (1:1) to receive SPP-004 or placebo ( n =14 each). Efficacy was evaluated using NPMDS for the full analysis set (FAS) during the DB-period (SPP-004 n =13, Placebo n =14) and the entire study period ( n =54). Safety evaluation focused on adverse events (AEs) in all 54 patients administered SPP-004. Results The primary endpoint, the proportion of patients who discontinued due to inadequate efficacy at 48 weeks, was lower in the SPP-004 group (15.4% [95% CI: 1.9-45.4%]) compared to the placebo group (50.0% [23.0-77.0%]). Over 80% of the SPP-004 group maintained efficacy (p=0.0486). All adverse drug reactions were mild, with no notable differences in AEs between groups. Conclusion These findings suggest that SPP-004 is safe and may provide therapeutic effect for LS symptoms.

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BACKGROUND: In Japan, the authorized period (2-4 h) between oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) and transurethral resection for non-muscle invasive bladder cancer (NMIBC) may restrict photodynamic diagnosis (PDD) usage. Therefore, this prospective, single-arm, phase III study aimed to evaluate the diagnostic accuracy and safety of PDD at an extended administration period (4-8 h). METHODS: From January 2022 to May 2023, 161 patients with NMIBC were enrolled from eight hospitals. The primary endpoint was the blue light (BL) sensitivity of pathologically positive biopsies. The secondary endpoints were a comparison of the specificity and positive and negative prediction rates under BL and white light (WL) conditions. RESULTS: A total of 1242 specimens comprising 337 histological NMIBC specimens were analyzed. BL-sensitivity was 95.3%. Its lower limit of 95% confidence interval (92.4-97.3%) exceeded the threshold (70%) of non-inferiority to authorized usage. Sensitivity and specificity were significantly higher and lower for BL than those for WL (95.3% vs. 61.1%, P < 0.001; 52.7% vs. 95.2%, P < 0.001), respectively. The positive and negative predictive rates were significantly lower and higher for BL than those for WL (42.9% vs. 82.7%, P < 0.001; 96.8% vs. 86.8%, P < 0.001), respectively. Of the 145 patients receiving 5-ALA, 136 (93.8%) and 75 (51.7%) experienced 377 adverse events and 95 adverse reactions, respectively, most of which were grade 1 or 2. CONCLUSION: For extended period, the efficacy of PDD for NMIBC was similar to that of authorized period, in terms of higher sensitivity and lower specificity compared with WL, and the safety was acceptable.

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PURPOSE: Oral administration of 5-aminolevulinic acid hydrochloride (5-ALA-HCl) has been reported to enhance the hypotensive effects associated with anesthetics, especially in elderly hypertensive patients treated with antihypertensive agents. The present study aimed to clarify the effects of antihypertensive-agent- and anesthesia-induced hypotension by 5-ALA-HCl in spontaneously hypertensive rats (SHRs). METHODS: We measured blood pressure (BP) of SHRs and normotensive Wistar Kyoto (WKY) rats treated with amlodipine or candesartan before and after administration of 5-ALA-HCl. We also investigated the change in BP following intravenous infusion of propofol and intrathecal injection of bupivacaine in relation to 5-ALA-HCl administration. FINDINGS: Oral administration of 5-ALA-HCl significantly reduced BP in SHRs and WKY rats with amlodipine and candesartan. Infusion of propofol significantly reduced BP in SHRs treated with 5-ALA-HCl. Intrathecal injection of bupivacaine significantly declined SBP and DBP in both SHRs and WKY rats treated with 5-ALA-HCl. The bupivacaine-induced decline in SBP was significantly larger in SHRs compared with WKY rats. CONCLUSION: These findings suggest that 5-ALA-HCl does not affect the antihypertensive agents-induced hypotensive effect, but enhances the bupivacaine-induced hypotensive effect, especially in SHRs, indicating that 5-ALA may contribute to anesthesia-induced hypotension via suppression of sympathetic nerve activity in patients with hypertension.

Abstract licence: CC BY-NC-ND

There are insufficient studies comparing the efficacy of aminolevulinic acid hydrochloride topical powder (ALA) photodynamic therapy (PDT) against Nocardia rubra cell wall skeleton (Nr-CWS) therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with human papillomavirus (HPV), especially for long-term efficacy. Patients with cervical LSIL and HPV infection were divided into 3 treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4 to 6 months and 12 months after the treatment. Among142 patients, patients received 51 ALA PDT and 41 patients received Nr-CWS. Another 50 patients who refused treatment were included in the Observers group. Four to six months or 12 months after treatment, there was significant difference between 3 groups in the clearance rate of HR-HPV infection and the complete remission (CR) rates of cervical LSIL; the CR rates of cervical LSIL in the ALA PDT group was significantly higher than the Nr-CWS group; but there was no significant difference between 2 groups in the clearance rate of HPV infection. The CR rates of cervical LSIL and the clearance rate of HPV infection in the ALA PDT group was significantly higher than the Observers group; the CR rates of cervical LSIL and the clearance rate of HPV infection in the Nr-CWS group was significantly higher than the Observers group; there was no significant difference in the recurrence rates in ALA PDT and Nr-CWS group after 12 months. Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. The effect of ALA PDT is similar to Nr-CWS in the clearance rate of HR-HPV infection. Compared to the Nr-CWS group, the CR rates of cervical LSIL were considerably greater in the ALA PDT group. The effect of ALA PDT in the clearance rate of HPV infection and CR rates of cervical LSIL was significantly higher than the follow-up group; Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. For cervical LSIL with HPV infection, ALA PDT is a very successful therapeutic method that is noninvasive.

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