These first-in-human, randomized, double-blind (sponsor unblinded), placebo-controlled studies evaluated oral ribitol in healthy adult volunteers to assess safety, tolerability, pharmacokinetics (PK), the effect of food on exposure, and the impact on cardiac repolarization (QTcF). Ribitol is an endogenous pentose alcohol and a precursor to CDP-ribitol, the substrate used by the fukutin‑related protein (FKRP) enzyme, which is deficient in Limb‑girdle muscular dystrophy Type R9 (LGMDR9). The clinical program reported here comprised single ascending dose, multiple‑dose (up to 6 days), food‑effect, and a dedicated QT study.
Across the single and multiple dosing regimens administered to healthy adults, ribitol was reported to be well tolerated. The source states that single doses and multiple oral doses over 6 days were administered without unexpected tolerability concerns in the healthy volunteer cohorts. The abstract did not provide a detailed adverse event table, incidence rates, or lab/safety parameter breakdown in this summary; those details were not reported in the source abstract.
Pharmacokinetic analyses showed dose‑proportional increases in ribitol exposure over the tested single‑dose range of 0.5 to 15 g. The apparent terminal half‑life (t½) of ribitol in plasma was reported as approximately 9–13 hours. These PK characteristics informed the therapeutic dosing proposed for patients: 9 g twice daily (BID) for those weighing >30 to ≤50 kg and 12 g BID for those weighing >50 kg, as noted in the abstract.
The PK profiles presented in the full article include mean plasma concentration–time plots for single oral solution doses across the tested range; the abstract indicates that plotted concentrations were not adjusted for endogenous plasma ribitol levels, and placebo group data show the magnitude and stability of endogenous levels over time. Specific PK parameter values beyond t½ (for example Cmax, AUC numbers, clearance, or volume of distribution) were not reported in the abstract summary provided here.
A dedicated food‑effect evaluation compared ribitol exposure when administered with a high‑fat meal versus the fasted state. The study found that a high‑fat meal did not materially affect overall oral bioavailability of ribitol. Based on those findings, ribitol may be administered without regard to food intake. The abstract does not provide the numerical fed/fasted ratios for Cmax or AUC in this summary; those specific values were not reported in the abstract.
A dedicated QT study evaluated the potential for ribitol to prolong cardiac repolarization, using QT interval corrected by Fridericia’s formula (QTcF) as the endpoint. The QT study employed a 21 g ribitol dose and included statistical modeling of change‑from‑baseline QTcF (ΔQTcF) across time points. The analysis excluded a concentration‑dependent QTcF prolongation and concluded that clinically significant QTcF prolongation was excluded across the range of observed ribitol exposures in the study, up to a maximum plasma concentration of 351.9 µg/mL.
Assay sensitivity in the dedicated QT study was demonstrated by inclusion of moxifloxacin, which produced the expected QT effect and thereby validated the study’s sensitivity to detect small QT changes. The abstract includes a description of the linear mixed‑effects model used to relate ΔQTcF to plasma concentration and other covariates; the modeled relationship indicated no positive concentration‑dependent increase in QTcF with increasing ribitol concentrations. The abstract does not reproduce full modeling coefficients or all time‑matched QT data beyond what was summarized here.
From the studies summarized in this source, orally administered ribitol was well tolerated in healthy adults, demonstrated dose‑proportional PK over 0.5–15 g with a t½ of 9–13 hours, showed no meaningful food effect with a high‑fat meal, and did not cause concentration‑dependent QTcF prolongation up to measured exposures of 351.9 µg/mL. These Phase I results support continued clinical development of ribitol as a therapeutic candidate for LGMDR9, where ribitol’s role as a precursor to CDP‑ribitol is intended to augment FKRP‑dependent glycosylation of alpha‑dystroglycan. The abstract concludes these data support further development; specific next steps, patient efficacy outcomes, and longer‑term safety in patient populations were not reported in this source.
The authors reported that at the time of analysis they were employees or contractors of BridgeBio Pharma Inc. and ML Bio Solutions Inc., the sponsors of the studies. No other conflicts of interest or financial relationships were reported in the abstract.
(Notes: Numerical PK parameters beyond those explicitly reported in the abstract and detailed adverse event tables, ancillary safety labs, or full modeling outputs are not provided in the source abstract and therefore are not included here.)