PET and MRI Imaging With Scopolamine at the Muscarinic M1 Receptor

NCT06014385 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 2000034723000
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the target occupancy (TO) of scopolamine at M1 Muscarinic Receptors in the brain after single I.V. doses of scopolamine, in healthy control subjects, using the radiotracer \[11C\]EMO (also known as \[11C\]LSN3172176).

Conditions

Muscarinic Receptor Occupancy

Outcome Measures

Primary Outcomes (1)

• Change in brain muscarinic receptor occupancy with [11C]LSN3172176 PET

  M1 Muscarinic receptor occupancy in the brain following a 15-minute IV infusion of scopolamine in healthy adult participants using PET scans.

  baseline and up to 48 hours post scopolamine infusion

Study Arms (2)

Scopolamine high dose

EXPERIMENTAL

The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer \[11C\]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 4.0 μg/kg scopolamine in 4-6 anticipated participants.

Drug: Scopolamine; Radiation: [11C]EMO ([11C]LSN3172176)

Scopolamine low dose

EXPERIMENTAL

The target occupancy (TO) of scopolamine at M1 will be evaluated using the radiotracer \[11C\]EMO and positron emission tomography (PET). TO will be measured following a 15-minute IV infusion of 2.0 μg/kg scopolamine in 0-2 anticipated participants.

Drug: Scopolamine; Radiation: [11C]EMO ([11C]LSN3172176)

Interventions

Scopolamine DRUG

TO will be measured following a 15-minute IV infusion of up to 2 dose levels of scopolamine: 4.0 μg/kg and 2.0 μg/kg

Scopolamine high dose; Scopolamine low dose

[11C]EMO ([11C]LSN3172176) RADIATION

A radiotracer specific for imaging M1 receptors. For each PET scan, up to 20 mCi of \[11C\]EMO i.v. will be administered twice, at baseline and post dosing with scopolamine.

Scopolamine high dose; Scopolamine low dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to give voluntary, written informed consent
• Have the ability to read and write, communicate effectively with the investigator and to comply with all study requirements, restrictions, and directions of the research staff.
• Male or female, aged Age 18 to 60 years inclusive, at screening.
• In good general health as evidenced by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests.

You may not qualify if:

• History or presence of clinically significant respiratory, GI, renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers.
• Laboratory tests with clinically significant abnormalities or positive urine toxicology, at screening.
• Abnormal and clinically significant ECG, as (as determined by the Investigator or his/her designee) at screening.
• Seropositive for hepatitis B, hepatitis C, and/or HIV
• Pregnancy or lactation
• Use of prescription medications within 14 days of scopolamine dosing. Exceptions may be allowed only if the medication's administration is deemed unlikely to impact the study result.
• Current or recent use (within 14 days) of scopolamine transdermal patch, for any reason (ex: for motion sickness).
• Use of drugs with anticholinergic properties within 14 days of scopolamine dosing, for example, belladonna alkaloids, first generation antihistamines, antidepressants (tricyclics and MAO inhibitors), phenothiazines and second generation antipsychotics (clozapine and olanzapine), amantadine and quinidine. Non-sedating antihistamines (e.g., loratadine) use is acceptable.
• Strong CYP3A4 inhibitors such as itraconazole and grapefruit juice should also not be taken within 14 days of receiving scopolamine. Use of CYP3A4 inducers (e.g., carbamazepine, rifampin) should not be taken within 21 days of scopolamine administration.
• Treatment with another investigational drug or other intervention within 30 days of the screening visit, or participation in another trial involving radiotracer administration within 1 week of dosing day.
• Current smoker (including any form of nicotine use)
• History of alcohol or drug abuse, within 2 years prior to screening, as determined by the investigator.
• Positive drug test at screening
• Blood donation within eight weeks of the start of the study. Subjects that confirm recent blood donation may reschedule for a later screening date.
• History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto).

Sponsors & Collaborators

• Yale University: lead
• Janssen Scientific Affairs, LLC: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06520, United States

Location

MeSH Terms

Interventions

Scopolamine; LSN3172176

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• David Matuskey, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: August 28, 2023
• Study Start: March 1, 2025
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: May 11, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)