PMID- 37738329
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240129
IS  - 1941-2703 (Electronic)
IS  - 1941-2711 (Linking)
VI  - 36
IP  - 6
DP  - 2023 Dec
TI  - A Phase I Study of TRK-250, a Novel siRNA-Based Oligonucleotide, in Patients with 
      Idiopathic Pulmonary Fibrosis.
PG  - 300-308
LID - 10.1089/jamp.2023.0014 [doi]
AB  - Purpose: TRK-250 is a novel single-stranded oligonucleotide carrying a human 
      Transforming growth factor-beta 1-targeting siRNA motif tethered by two proline 
      linkers. Nonclinical studies have shown that TRK-250 may have potency to prevent 
      the progression of pulmonary fibrosis. Herein, a phase I study was conducted to 
      investigate the safety and pharmacokinetics (PKs) of TRK-250 in patients with 
      idiopathic pulmonary fibrosis (IPF). Method: In the phase I study, 34 IPF 
      patients were partially randomized to receive a placebo or TRK-250 in 4 single 
      doses of 2, 10, 30, and 60 mg or multiple rising doses of 10, 30, and 60 mg once 
      per week for 4 weeks by oral inhalation. For both the single- and multiple-dose 
      studies, the primary endpoint was safety, and the secondary endpoint was PKs. 
      Result: In all IPF patients who orally inhaled TRK-250, no significant 
      drug-related adverse events (AEs) were observed. The AEs were mild or moderate, 
      except for one severe case with acute exacerbation. One of the more common AEs 
      was coughing. One patient discontinued treatment before the last dose because of 
      coughing. There were no medically important findings related to safety endpoints 
      based on clinical laboratory data (clinical chemistry, hematology, or 
      urinalysis), vital signs data, electrocardiogram data, physical examination 
      findings, pulse oximetry data, spirometry data, or diffusing capacity of the lung 
      for carbon monoxide data. All the bioanalytical results of PKs in the blood were 
      below the lower limit of quantification. Conclusions: Both the single and 
      multiple doses of TRK-250 were safe and well tolerated in this first study done 
      in IPF patients. Furthermore, TRK-250 was not detected in the systemic 
      circulation following inhalation, indicating low or virtually nonexistent 
      systemic exposure. This study is registered at ClinicalTrials.gov with identifier 
      number NCT03727802.
FAU - Doi, Hiroyuki
AU  - Doi H
AUID- ORCID: 0009-0007-3343-2319
AD  - Clinical Research Department, Toray Industries, Inc., Tokyo, Japan.
FAU - Atsumi, Jun
AU  - Atsumi J
AD  - Clinical Research Department, Toray Industries, Inc., Tokyo, Japan.
FAU - Baratz, David
AU  - Baratz D
AD  - Pulmonary Associates, Phoenix, Arizona, USA.
FAU - Miyamoto, Yohei
AU  - Miyamoto Y
AD  - Clinical Research Department, Toray Industries, Inc., Tokyo, Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT03727802
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230922
PL  - United States
TA  - J Aerosol Med Pulm Drug Deliv
JT  - Journal of aerosol medicine and pulmonary drug delivery
JID - 101475057
RN  - 0 (RNA, Small Interfering)
MH  - Humans
MH  - RNA, Small Interfering
MH  - Administration, Inhalation
MH  - *Idiopathic Pulmonary Fibrosis/drug therapy/genetics
MH  - Lung
MH  - Cough
MH  - Double-Blind Method
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Phase I Study
OT  - TGF-beta1
OT  - idiopathic pulmonary fibrosis
OT  - inhalation
OT  - siRNA
EDAT- 2023/09/22 18:42
MHDA- 2023/12/17 09:44
CRDT- 2023/09/22 13:53
PHST- 2023/12/17 09:44 [medline]
PHST- 2023/09/22 18:42 [pubmed]
PHST- 2023/09/22 13:53 [entrez]
AID - 10.1089/jamp.2023.0014 [doi]
PST - ppublish
SO  - J Aerosol Med Pulm Drug Deliv. 2023 Dec;36(6):300-308. doi: 
      10.1089/jamp.2023.0014. Epub 2023 Sep 22.