Receptor Occupancy of LB-102 Using Positron Emission Tomography (PET) in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT04588129
• Recruitment Status: Completed
• First Posted: October 19, 2020
• Last Update Posted: May 4, 2022
• Sponsor: LB Pharmaceuticals Inc.
• Collaborator: Washington University School of Medicine
• Information provided by (Responsible Party): LB Pharmaceuticals Inc.

Study Description

Brief Summary:

This is an open label study in 4 cohort of 4 healthy volunteers each designed to evaluate the dopamine receptor occupancy of LB-102 at various doses and timepoints.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: LB-102	Phase 1

Detailed Description:

This is a Phase 1, open label study designed to evaluate the dopamine receptor occupancy in healthy subjects. There will be 4 cohorts consisting of 4 subjects each. Eligible subjects will receive 1 or 2 doses of LB-102 on Day 1: subjects in the final cohort will be dosed for 5 days BID (ie twice/day) on an inpatient basis. This will be an open label study. Blood samples for pharmacokinetic (PK) and safety assessments will be collected at screening, immediately pre-dose, and during/before/after PET scan. Subjects enrolled in the inpatient cohort will be monitored daily. Follow-up after discharge will consist of a phone call the evening of discharge and the next day to check on subjects. This will be an adaptive study and doses in cohorts 2-4 will be determined after PET data from Cohort 1 are obtained.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: An Open Label Positron Emission Tomography (PET) Study to Evaluate Dopamine Receptor Occupancy of LB-102 Administered Orally to Healthy Subjects
• Actual Study Start Date: January 5, 2021
• Actual Primary Completion Date: September 17, 2021
• Actual Study Completion Date: November 15, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: LB-102 50 mg, single dose Cohort 1; LB-102 (N-Methyl amisulpride) formulated capsule will be administered orally once daily for one day in 4 subjects.	Drug: LB-102; (N-Methyl amisulpride)
Experimental: LB-102 100 mg, single dose Cohort 2; LB-102 (N-Methyl amisulpride) formulated capsule will be administered orally once daily for one day in 4 subjects.	Drug: LB-102; (N-Methyl amisulpride)
Experimental: LB-102 75 mg, single dose Cohort 3; LB-102 (N-Methyl amisulpride) formulated capsule will be administered orally once daily for one day in 4 subjects.	Drug: LB-102; (N-Methyl amisulpride)
Experimental: LB-102 100 & 50 mg, multiple dose Cohort 4; LB-102 (N-Methyl amisulpride) formulated capsule will be administered orally once daily for four days in 4 subjects: 2 subjects @ 100 mg and 2 subjects @ 50 mg.	Drug: LB-102; (N-Methyl amisulpride)

Outcome Measures

Primary Outcome Measures :

1. Brain Receptor Occupancy as Measured by Positron Emission Tomography [ Time Frame: 2.5 hours post LB-102 dose ]
   PET scan of D2/D3 receptor occupancy using raclopride as a tracer
2. Brain Receptor Occupancy as Measured by Positron Emission Tomography [ Time Frame: 7.5 hours post LB-102 dose ]
   PET scan of D2/D3 receptor occupancy using raclopride as a tracer
3. Brain Receptor Occupancy as Measured by Positron Emission Tomography [ Time Frame: 23.5 hours post LB-102 dose ]
   PET scan of D2/D3 receptor occupancy using raclopride as a tracer

Secondary Outcome Measures :

1. Safety and Tolerability as Measured by Reported Adverse Events [ Time Frame: Up to 14 days ]
   Measurement of clinical events as determined by medical staff reporting

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 at screening visit. Competent to provide informed consent.

Subjects must be in good general health as determined by medical history and physical examination with no clinically significant medical findings and no history of significant medical disease (e.g., cardiovascular, pulmonary, renal, etc.) or acute condition with the past 30 days, as determined by the study investigators.

Have normal clinical laboratory test results and ECG, which are not considered to be clinically significant by the Investigator.

Exclusion Criteria:

1. Are pregnant or lactating.
2. Have a history or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological or psychological/psychiatric disorders which, in the opinion of the Investigator, increases the risk of the study drug or may confound the interpretation of study measures.
3. Clinically significant abnormal findings on physical examination or vital signs as determined by Investigator.
4. Individuals with pacemakers, aneurysm clips, shrapnel, or other restricted implanted metallic devices will be excluded from study. All subjects complete the standard MRI screening questionnaire prior to MRI.
5. History or presence of psychiatric or neurological disease or condition, as determined by the Investigator.
6. History of seizures.
7. Subject with any history or current evidence of suicidal behavior.
8. Unwilling to complete any planned study assessments.
9. Have a history of blood donation in excess of 500 mL of blood within 30 days prior to Screening.
10. Have received treatment with an investigational drug or device within 30 days prior to Screening.
11. Have a positive test for Human Immunodeficiency Virus (HIV) antibodies 1 and 2, Hepatitis B Surface Antigen (HBsAg) or Hepatitis C Virus (HCV) antibody.
12. Any subject who is known to be allergic to the study drug or any components of the study drug.
13. The subject has a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c (HbA1c) ≥ 6.5% at Screening.
14. The subject has a history of QT prolongation or dysrhythmia or a family history of prolonged QT interval or sudden death.

15. Clinically significant abnormal finding on ECG (electrocardiogram) and/or evidence of any of the following cardiac conduction abnormalities at Screening:

    1. Heart rate < 40 bpm and > 100 bpm (based on the ECG reading)
    2. QTcF interval > 450 msec for males and females
    3. PR interval ≥ 200 msec
    4. Intraventricular conduction delay with QRS duration > 120 msec
    5. Evidence of second- or third-degree atrioventricular block (AVB)
    6. Electrocardiographic evidence of complete left bundle branch block (LBBB), complete right bundle branch block (RBBB), or incomplete LBBB

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

LB Pharmaceuticals Inc.

Washington University School of Medicine

Investigators

• Principal Investigator: Dean Wong, PhD; Washington University School of Medicine

More Information

Additional Information:

Corporate Website 

• Responsible Party: LB Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT04588129
• Other Study ID Numbers: LB-102-002
• First Posted: October 19, 2020
• Last Update Posted: May 4, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders