Trial reportBritish journal of clinical pharmacology2019
A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier.
Trial report in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- A phase 1 healthy male volunteer single escalating dose study of the pharmacokinetics and pharmacodynamics of risdiplam (RG7916, RO7034067), a SMN2 splicing modifier.British journal of clinical pharmacology · 2019Trial
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Extracellular vesicles as biomarkers of disease progression and therapeutic response in patients with spinal muscular atrophy.Molecular therapy. Advances · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- MyomiR Networks in Spinal Muscular Atrophy: Associations With Clinical Severity and Treatment Response.Molecular neurobiology · 2026Article
- RNA biomarkers in spinal muscular atrophy: enhancing pathogenesis understanding and guiding precision medicine.Cellular and molecular life sciences : CMLS · 2026Review
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- What Do Oral Drugs Really Look Like? Dose Regimen, Pharmacokinetics, and Safety of Recently Approved Small-Molecule Oral Drugs.Journal of medicinal chemistry · 2025Review
- Pharmacokinetics of therapies approved for spinal muscular atrophy: A narrative review of current evidence.The Journal of international medical research · 2025Review
- Overcoming bioanalytical challenges during the development of risdiplam for the treatment of spinal muscular atrophy.Bioanalysis · 2025Article
- Large-scale analysis of small molecule-RNA interactions using multiplexed RNA structure libraries.Communications chemistry · 2024Article
- Optimization of base editors for the functional correction of SMN2 as a treatment for spinal muscular atrophy.Nature biomedical engineering · 2024Article
- Neurodegenerative Diseases: New Hopes and Perspectives.Current molecular medicine · 2024Review
- Molecular Biomarkers for the Diagnosis, Prognosis, and Pharmacodynamics of Spinal Muscular Atrophy.Journal of clinical medicine · 2023Review
- New therapies for spinal muscular atrophy: where we stand and what is next.European journal of pediatrics · 2023Review
- Estimation of FMO3 Ontogeny by Mechanistic Population Pharmacokinetic Modelling of Risdiplam and Its Impact on Drug-Drug Interactions in Children.Clinical pharmacokinetics · 2023Article
- Experimental Medicine Approaches in Early-Phase CNS Drug Development.Advances in neurobiology · 2023Article
- Identifying Biomarkers of Spinal Muscular Atrophy for Further Development.Journal of neuromuscular diseases · 2023Article
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsRisdiplam (RG7916, RO7034067) is an orally administered, centrally and peripherally distributed, survival of motor neuron 2 (SMN2) mRNA splicing modifier for the treatment of spinal muscular atrophy (SMA). The objectives of this entry-into-human study were to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of risdiplam, and the effect of the strong CYP3A inhibitor itraconazole on the PK of risdiplam in healthy male volunteers.
methodsPart 1 had a randomized, double-blind, adaptive design with 25 subjects receiving single ascending oral doses of risdiplam (ranging from 0.6-18.0 mg, n = 18) or placebo (n = 7). A Bayesian framework was applied to estimate risdiplam's effect on SMN2 mRNA. The effect of multiple doses of itraconazole on the PK of risdiplam was also assessed using a two-period cross-over design (n = 8).
resultsRisdiplam in the fasted or fed state was well tolerated. Risdiplam exhibited linear PK over the dose range with a multi-phasic decline with a mean terminal half-life of 40-69 h. Food had no relevant effect, and itraconazole had only a minor effect on plasma PK indicating a low fraction of risdiplam metabolized by CYP3A. The highest tested dose of 18.0 mg risdiplam led to approximately 41% (95% confidence interval 27-55%) of the estimated maximum increase in SMN2 mRNA.
conclusionsRisdiplam was well tolerated and proof of mechanism was demonstrated by the intended shift in SMN2 splicing towards full-length SMN2 mRNA. Based on these data, Phase 2/3 studies of risdiplam in patients with SMA are now ongoing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.