A 3-way Cross-over Study on the Effects of QRL-101 on Transcranial Magnetic Stimulation and Nerve Excitability in Healthy Participants

A Phase I, Randomized, Double-blind, Placebo-controlled, 3-way Cross-over Study to Assess the Pharmacodynamic Effects of Two-dose Levels of QRL-101 on Transcranial Magnetic Stimulation and Nerve Excitability Threshold Tracking in Healthy Participants

This is a phase I, prospective, single-center, randomized, double-blind, placebo-controlled, three-way cross-over study to evaluate the safety and tolerability of QRL-101 and investigate the pharmacodynamic effects of two dose levels of QRL-101 on transcranial magnetic stimulation (TMS) and nerve excitability threshold tracking (NETT) in healthy participants.

After screening and training, participants will be randomized to one of six treatment sequences of William's square balanced for first-order carry-over design consisting of two doses of QRL-101 or placebo, with at least seven days between each treatment.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: QRL-101 Dose A; Drug: QRL-101 Dose B; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • Centre For Human Drug Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males and postmenopausal women between the ages ≥ 18 and ≤ 55.
2. BMI ≥ 18.0 and ≤ 32.0 kg/m2, and body weight ≥ 50 kg, at screening.
3. Willing and able to practice effective contraception from the screening through at least 2 days after their last dose of study treatment.
4. Participants must be able to communicate effectively (in Dutch) with the study personnel and be willing to comply with the requirements of the study.

Exclusion Criteria:

1. Evidence of any acute or chronic disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study.
2. History or presence of conditions which, in the judgment of the investigator, are known to interfere with drug absorption, distribution, metabolism, or excretion.
3. History or presence of conditions which might increase the risk of performing TMS (e.g., epilepsy, febrile seizures, intracranial mass lesion, hydrocephalus, clinically significant head injury or trauma, metal objects in the brain or skull, cochlear implant or a deep brain stimulation device)
4. Any condition that could interfere with the quality of, or ability to perform, TMS (e.g., an abnormal sleeping pattern, unremovable dreadlocks or hairpieces, or a resting motor threshold (rMT) of more than 75%.

*Other inclusion and exclusion criteria may apply*

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1; Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over	Drug: QRL-101 Dose A; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: QRL-101 Dose B; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: Placebo; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.
Experimental: Treatment Group 2; Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over	Drug: QRL-101 Dose A; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: QRL-101 Dose B; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: Placebo; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.
Experimental: Treatment Group 3; Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over	Drug: QRL-101 Dose A; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: QRL-101 Dose B; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: Placebo; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.
Experimental: Treatment Group 4; Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over	Drug: QRL-101 Dose A; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: QRL-101 Dose B; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: Placebo; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.
Experimental: Treatment Group 5; Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over	Drug: QRL-101 Dose A; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: QRL-101 Dose B; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: Placebo; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.
Experimental: Treatment Group 6; Participants will be randomized into 1 of 6 treatment sequences in a 3-way cross-over	Drug: QRL-101 Dose A; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: QRL-101 Dose B; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.; Drug: Placebo; All participants will receive three single-dose oral administrations in randomized order, scheduled across three separate study visits, with a 7-day washout period between each visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Single pulse TMS-EMG motor evoked potential (MEP) amplitude (μV) compared to placebo	To compare two dose levels of QRL-101 versus placebo on cortical excitability	3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.
mNETT strength-duration time constant (SDTC) compared to placebo SDTC	To compare two dose levels of QRL-101 versus placebo on peripheral motor nerve excitability	3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other Single pulse TMS-EMG MEP parameters	To compare two dose levels of QRL-101 versus placebo on cortical excitability	3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.
pEEG: power in the alpha frequency bands in resting state with eyes open and closed	To compare two dose levels of QRL-101 versus placebo on spontaneous brain activity measured by resting state pharmaco-encephalography (pEEG)	3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.
Incidence of AEs and SAEs	Absolute values and changes from baseline values in vital signs, clinical laboratory tests, and ECG parameters	3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.
Plasma QRL-101 concentrations	AUC0-24	3 study periods, with a washout period of at least 7 days between each visit. Each study period consists of 2 nights and 1 study day.

Collaborators and Investigators

• Sponsor: QurAlis Corporation
• Collaborators: Centre for Human Drug Research, Netherlands
• Investigators: Principal Investigator: Philip Kremer, PharmD, MD, PhD, Centre For Human Drug Research; Principal Investigator: K. (Kaye) de Cuba,, MD, Centre For Human Drug Research

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2024
• Primary Completion (Actual): December 24, 2024
• Study Completion (Actual): December 24, 2024

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Actual): November 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: QRL-101
• Other Study ID Numbers: QRL-101-05

Drug and device information, study documents

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