Pharmacokinetics, Safety, and Tolerability of Anti‐miR‐17 Oligonucleotide RGLS4326 in Healthy Adult Subjects.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of polycystic kidney disease in adults and is characterized by progressive renal cyst formation and enlargement of the kidneys. The expression of microRNA‐17 (miR‐17) family is increased in kidney samples from ADPKD patient...
| Publicado en: | Journal of Clinical Pharmacology Vol. 66; no. 5; pp. 1 - 17 |
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| Autores principales: | , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
May2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=194009249&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 194009249 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: May2026 vid: 66 iid: 5 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 194009249 194009249 194009249 10.1002/jcph.70207 194009249 ppf: 1 ppct: 16 formats: tig: atl: Pharmacokinetics, Safety, and Tolerability of Anti‐miR‐17 Oligonucleotide RGLS4326 in Healthy Adult Subjects. aug: au: Owen, Tate Cole, Izaiah Drygin, Denis Valencia, Tania Lee, Edmund C. Carlson, Morgan Ruff, Laura Padgett, Claire Cremer, Karl Wright, Timothy M. Garg, Rekha Klassen, Preston Kamel, Amin affil: Regulus Therapeutics, A Novartis Company, San Diego CA, , USA sug: subj: Polycystic Kidney, Autosomal Dominant Drug Therapy MicroRNA Antagonists and Inhibitors Nucleotides Pharmacokinetics Nucleotides Therapeutic Use Nucleotides Administration and Dosage Patient Safety Evaluation Drug Tolerance Evaluation Injections, Subcutaneous Human Gene Expression Drug Effects Placebos Descriptive Statistics Nucleotides Urine Nucleotides Blood Enzyme-Linked Immunosorbent Assay Drug Toxicity Prevention and Control Biological Markers Analysis Nucleotides Pharmacodynamics Data Analysis Software Funding Source ab: Autosomal dominant polycystic kidney disease (ADPKD) is the most common form of polycystic kidney disease in adults and is characterized by progressive renal cyst formation and enlargement of the kidneys. The expression of microRNA‐17 (miR‐17) family is increased in kidney samples from ADPKD patients. RGLS4326 is a short oligonucleotide inhibitor of miR‐17 that preferentially distributes to the kidney and displaces miR‐17 from translationally active polysomes. Here, we present pharmacokinetics (PK), safety, and tolerability of RGLS4326 from phase 1 single‐ascending dose (SAD) and multiple‐ascending‐dose (MAD) studies in healthy subjects. Healthy adult subjects received a placebo or a single‐ascending subcutaneous dose of 0.05, 0.2, 0.6, 2, and 6 mg/kg or a multiple‐ascending dose of 0.1, 0.3, and 1 mg/kg (four doses, once every 2 weeks). In the SAD study, plasma exposures increased in a dose‐proportional manner across the dose range. Geometric mean t1/2 values ranged from ≈3 to 8 h after subcutaneous injection to the abdomen, with longer t1/2 values of ≈11 to 20 h and lower plasma exposures after subcutaneous injection to the upper arm or thigh. Urinary excretion increased with dose and ranged from 37% to 63%. In the MAD study, the mean elimination t1/2 ranged from ≈5 to 7 h and plasma exposures increased in proportion to the dose range. The mean dose excreted in the urine for the 0.1 and 0.3 mg/kg doses was 35.2% to 39.3% compared to 46.5% to 48.1% for the 1.0 mg/kg dose. RGLS4326 was generally well tolerated, and no dose limiting treatment emergent adverse events were observed. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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