Clinical trial NCT06681441: A 3-way Cross-over Study on the Effects of QRL-101 on Transcranial Magnetic Stimulation and Nerve Excitability in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: QRL-101
Lead sponsor: QurAlis Corporation
Sponsor class: INDUSTRY
Collaborators: name: Centre for Human Drug Research, Netherlands
First posted: 2024-11-08
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a randomized, double-blind, placebo-controlled, 3-way cross-over, single-dose study to investigate the effects of QRL-101 on TMS-EMG-EEG, mNETT, and pEEG in healthy participants.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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\*

Primary outcomes:
measure: Single pulse TMS-EMG motor evoked potential (MEP) amplitude (μV) compared to placebo
timeFrame: 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.
measure: mNETT strength-duration time constant (SDTC) compared to placebo SDTC
timeFrame: 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 outcomes:
measure: Other Single pulse TMS-EMG MEP parameters
timeFrame: 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.
measure: pEEG: power in the alpha frequency bands in resting state with eyes open and closed
timeFrame: 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.
measure: Incidence of AEs and SAEs
timeFrame: 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.
measure: Plasma QRL-101 concentrations
timeFrame: 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.
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Centre for Human Drug Research
Study officials:
affiliation: Centre for Human Drug Research
name: Philip Kremer, PharmD, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Human Drug Research
name: K. (Kaye) de Cuba,, MD
role: PRINCIPAL_INVESTIGATOR
References: