Study Designed to Evaluate the Safety, Tolerability, and PK of RAP-219 Formulated as an Long Acting Injectable.

A Phase 1, Double-blind, Placebo-controlled, Single- and Multiple-dose Study of the Safety, Tolerability, and Pharmacokinetics of RAP-219 Administered as a Long-acting Injectable to Healthy Participants

This is a Phase 1, double-blind, placebo-controlled, 5-cohort study evaluating the pharmacokinetics (PK), safety, and tolerability of RAP-219-LAI in healthy participants aged 18 to 65 years. Assessment of up to four single-dose cohorts will characterize the PK profile of up to four ascending dose levels and evaluate dose proportionality. One multiple-dose cohort will characterize the accumulation profile of RAP-219-LAI.

The study includes a Screening Period of up to 28 days (Day -28 to Day -1) for participants in all cohorts. Cohorts 1, 2, 3, and 4 will include admission on Day -1, a single dosing day (Day 1), a 28-day inpatient and outpatient Treatment Period (Day 1 to Day 28), and a 28-day Follow-up Period (Day 29 to Day 56). Cohort 5 will include admission on Day -1 and Day 28, two dosing days (Day 1 and Day 29), a 56-day inpatient and outpatient Treatment Period (Day 1 to Day 56), and a 28-day Follow-up Period (Day 57 to Day 84).

Up to 60 participants are planned to be enrolled in this study, with 12 participants per cohort randomized in a 3:1 ratio to receive RAP-219-LAI or placebo.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Drug: RAP-219 or Placebo

Detailed Description

Participants will be randomized to receive a single dose of RAP-219-long acting injectable (LAI) (RAP-219-LAI) nanosuspension or placebo (Cohort 1, Cohort 2, Cohort 3, and Cohort 4), or 2 doses of RAP-219-LAI or placebo (Cohort 5) 28 days apart. A starting dose of 2.5 mg for Cohort 1 was chosen based on reviews of the preclinical data, clinical trials data and PK modelling and simulation. A sentinel group of 2 participants will be dosed and monitored for 24 hours. The rest of that cohort (8) will be dosed if there are no safety concerns noted with the sentinel group. A dose escalation committee (DEC) will review the safety and available PK data for cohort 1 and make a determination on the dose for Cohort 2. The DEC will review the data for subsequent cohorts and advise on does as well as study progression based on the emerging and cumulative safety and PK data.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rapport Medical; Phone Number: 857 323 9048; Email: RAP-219-FOS@rapportrx.com

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • CMAX Clinical Research
    • Contact: Dr. Thomas Polasek; Phone Number: +61 458 162 715; Email: Thomas.Polasek@cmax.com.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to provide written informed consent to participate in the study and comply with all aspects of the protocol
2. Age 18 to 65 years, inclusive, at Screening
3. Medically healthy, with no current medical or psychiatric conditions, or those that the participant has been diagnosed with or received treatment for in the past 1 year, or clinically significant abnormalities, as determined by the PI or delegate based on the participant's medical history, physical examination, vital signs, ECG, and laboratory evaluations

Exclusion Criteria:

1. Pregnant or breastfeeding, or intending to become pregnant during the course of the study
2. Skin conditions affecting abdominal injection site or any condition or characteristic that may prevent assessment of injection site reactions (ISRs)
3. Inadequate venous access or unsuitable veins for venipuncture
4. Donated blood or experienced significant blood loss (greater than or equals to 450 millilitres) within 12 weeks, donated bone marrow or peripheral stem cells within 90 days, or donated plasma within 4 weeks prior to Day 1.
5. History of malignancy, with the exception of non-melanoma skin cancer or cancer curatively treated greater than or equals to 5 years prior to Screening without evidence of recurrence
6. Recent history or current substance abuse
7. Consumption of liquids or foods containing Seville oranges, grapefruit, lime, pomegranate, or star fruit from 7 days prior to Day 1, or poppy seed from 3 days prior to Day 1 (all cohorts)
8. Unable or unwilling to refrain from strenuous exercise from 3 days prior to Day 1 and during the inpatient periods through the end of the study
9. History of any illness, any medical or psychiatric condition, or laboratory abnormality that, in the opinion of the PI or delegate, might prevent the participant from completing the study, pose a risk to the participant, or confound the results of the study
10. Any non-negative serology results for hepatitis B surface antigen, hepatitis C antibody, or HIV antigen and antibody.
11. Any surgical procedure within 3 months prior to Screening from which a full recovery was not made and/or with sequelae that may impact study procedures/outcomes and/or safety, as judged by the PI or delegate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: RAP-219 or Placebo; Route of Administration: Subcutaneous injection
Experimental: Cohort 2	Drug: RAP-219 or Placebo; Route of Administration: Subcutaneous injection
Experimental: Cohort 3	Drug: RAP-219 or Placebo; Route of Administration: Subcutaneous injection
Experimental: Cohort 4	Drug: RAP-219 or Placebo; Route of Administration: Subcutaneous injection
Experimental: Cohort 5	Drug: RAP-219 or Placebo; Route of Administration: Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax)	Up to 84 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: Adverse Events (AEs)	Up to 112 days

Collaborators and Investigators

• Sponsor: Rapport Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): October 5, 2027

Study Registration Dates

• First Submitted: October 16, 2026
• First Submitted That Met QC Criteria: November 2, 2026
• First Posted (Actual): November 6, 2026

Study Record Updates

• Last Update Posted (Actual): November 6, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: RAP-219-LAI-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes