A Phase 2 Safety, Tolerability, PK, and Efficacy Study of CS-1103 Following Fentanyl Challenge With Naloxone Blockade

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of a Single Dose of Intravenous CS 1103 Following a Single Intravenous Dose of Fentanyl in Healthy Subjects With Naloxone Blockade

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of CS-1103 (1,000 mg), given by intravenous (IV) infusion in healthy participants in the presence of a clinically relevant dose of fentanyl (200 μg, IV), with naloxone blockade (400 μg, IV).

Study Overview

• Status: Recruiting
• Conditions: Fentanyl Overdose; Fentanyl Poisoning
• Intervention / Treatment: Drug: Sterile Saline; Drug: CS-1103; Drug: Naloxone Hydrochloride; Drug: Fentanyl

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Piercen Oliver, Ph.D.; Phone Number: 617-621-8500; Email: poliver@clearsci.com
• Study Contact Backup: Name: Anna Del Rosario, B.S.; Phone Number: 617-621-8500; Email: adelrosario@clearsci.com

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Recruiting
      • California Clinical Trials Medical Group
      • Contact: Lev Gertsik, M.D.; Phone Number: 888-228-7425; Email: study.losangeles@parexel.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Major Inclusion Criteria:

1. Healthy participants aged 18 to 55 years, inclusive;
2. Have prior experience with opioids, such as from a dental procedure, chronic pain management, or previous inpatient surgical procedure;
3. A body mass index between 18.0 to 30.0 kg/m2, inclusive, and a minimum body weight of 56 kg;
4. Females must not be lactating and must have a negative pregnancy test during screening and admission.

Major Exclusion Criteria:

1. Estimated glomerular filtration rate <90 mL/min/1.73 m2;
2. History of cardiovascular disease;
3. History of any clinically important disease or disorder which, in the opinion of the Investigator, may interfere with safe study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants receive naloxone blockade (400 μg, IV), followed by fentanyl (200 μg, IV), followed by placebo (saline).	Drug: Sterile Saline; Sterile Saline for intravenous administration; Drug: Naloxone Hydrochloride; Naloxone for intravenous administration; Drug: Fentanyl; Fentanyl for intravenous administration
Active Comparator: Active; Participants receive naloxone blockade (400 μg, IV), followed by fentanyl (200 μg, IV), followed by CS-1103 (1,000 mg, IV).	Drug: CS-1103; CS-1103 for intravenous administration; Drug: Naloxone Hydrochloride; Naloxone for intravenous administration; Drug: Fentanyl; Fentanyl for intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time course of CS-1103 blood and urine concentrations	Measurement of plasma and urine concentrations of CS-1103	48 hours
Number of participants with CS-1103-related adverse events (AEs) assessed by physical examinations	Physical examinations	3 days plus follow-up on Day 10
Number of participants with CS-1103-related adverse events (AEs) assessed by vital signs	Blood pressure, pulse rate, respiratory rate, oxygen saturation, and body temperature	3 days plus follow-up on Day 10
Number of participants with CS-1103-related adverse events (AEs) assessed by laboratory parameters	Clinical chemistry, hematology, coagulation, and urinalysis	3 days plus follow-up on Day 10
Number of participants with CS-1103-related adverse events (AEs) assessed by electrocardiograms (ECGs)	Digital 12-lead electrocardiograms (ECGs). Any correlation between CS-1103 plasma concentrations and changes in QT intervals will be noted	3 days plus follow-up on Day 10
Time course and magnitude of urine excretion of fentanyl	Measurement of concentration of fentanyl in urine	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of CS-1103 and fentanyl on QT interval	Concentration-QT correlation performed on baseline-corrected QTcF time-matched with PK for fentanyl and CS-1103 in plasma	48 hours
Effect of CS-1103 on the naloxone plasma and urine PK, if any	Measurement of standard urine and plasma PK parameters between placebo and CS-1103 treated participants	48 hours

Collaborators and Investigators

• Sponsor: Clear Scientific, Inc.
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Xinhua Li, Ph.D., Clear Scientific, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Piperidines; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Fentanyl; Naloxone
• Other Study ID Numbers: CS-1103-03; 5UG3DA059286 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No