Positron Emission Tomography (PET) Study Investigating Dopamine and Serotonin Receptor Occupancy After Multiple Oral Dosing of Lu AF35700

NCT02333487 | Completed Phase 1 Results

• 1 other identifier: 15859A
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this PET study is to verify the binding of Lu AF35700 after multiple oral dosing at the dopamine and the serotonin receptors in male patients with schizophrenia.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (6)

• Emax D1 Dopamine

  Maximal target occupancy (Emax) on the D1 dopamine receptor using PET with \[11C\]-NNC 112 tracer compound. The relationship between systemic exposure of Lu AF35700 and D1 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.

  Change from baseline to 344 hours post last dose

• EC50 D1 Dopamine

  Plasma concentration which gives 50% of Emax (EC50) The relationship between systemic exposure of Lu AF35700 and D1 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.

  Change from baseline to 344 hours post last dose

• Emax D2 Dopamine

  Maximal target occupancy (Emax) on the D2 dopamine receptor using PET with \[11C\]-Raclopride tracer compound. The relationship between systemic exposure of Lu AF35700 and D2 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Emax was estimated using one model for all post-baseline scans combined. No statistical testing was performed.

  Change from baseline to 344 hours post last dose

• EC50 D2 Dopamine

  Plasma concentration which gives 50% of Emax (EC50) The relationship between systemic exposure of Lu AF35700+Lu AF36152 and D2 dopamine occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.

  Change from baseline to 344 hours post last dose

• Emax 5-HT6 Serotonin

  Maximal target occupancy (Emax) on the 5-HT6 receptor using PET with \[11C\]-Lu AE60157 as tracer compound. The relationship between systemic exposure of Lu AF35700+Lu AF36152 and 5-HT6 occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Emax was estimated using one model for all post-baseline scans combined. No statistical testing was performed.

  Change from baseline to 344 hours post last dose

• EC50 5-HT6 Serotonin

  Plasma concentration which gives 50% of Emax (EC50) The relationship between systemic exposure of Lu AF35700+Lu AF36152 and 5\_HT6 serotonin occupancy was investigated using an Emax model containing the regression parameters maximal target occupancy (Emax) and plasma concentration which gives 50% of Emax (EC50). Both Emax and EC50 were estimated using one model for all post-baseline scans combined. No statistical testing was performed.

  Change from baseline to 344 hours post last dose

Study Arms (3)

Lu AF35700 (Group D1)

EXPERIMENTAL

Up to 3 PET scans, besides baseline scan, using \[11C\]-NNC 112 tracer to detect D1 dopamine receptor occupancy before and after multiple oral dosing of Lu AF35700

Drug: Lu AF35700

Lu AF35700 (Group D2)

EXPERIMENTAL

Up to 3 PET scans, besides baseline scan, using \[11C\]-Raclopride to detect D2 dopamine receptor occupancy before and after multiple oral dosing of Lu AF35700

Drug: Lu AF35700

Lu AF35700 (Group 5-HT6)

EXPERIMENTAL

Up to 3 PET scans, besides baseline scan, using \[11C\]- Lu AE60157 tracer to detect 5-HT6 (5-hydroxytryptamine-6) receptor occupancy before and after multiple oral dosing of Lu AF35700

Drug: Lu AF35700

Interventions

Lu AF35700 DRUG

5 mg tablets for oral administration

Lu AF35700 (Group 5-HT6); Lu AF35700 (Group D1); Lu AF35700 (Group D2)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• The patient is a man aged between ≤18 and ≥60 years
• BMI of ≥19 kg/m2 to ≤ 37 kg/m2
• The patient has a primary diagnosis of schizophrenia according to DSM-5™ (code 295.90)
• The patient has a Clinical Global Impression - Severity of Illness (CGI-S) score ≤ 4 (moderately ill) at screening and safety baseline
• The patient is currently under oral therapy with one or more of the antipsychotic medications listed in Appendix II.
• The patient has a Positive and Negative Syndrome Scale (PANSS) total score ≤ 80
• The patient has a score of ≤ 4 (moderate) on the following PANSS items at screening and at safety baseline: P7 (hostility), G8 (uncooperativeness)

You may not qualify if:

• The patient experienced an acute exacerbation requiring hospitalization within the last 3 months.
• The patient experienced an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 4 weeks.
• The patient has a diagnosis or history of substance use disorder (except nicotine) according to DSM-5-TR® criteria ≤3 months prior to screening
• The patient is at significant risk of harming himself or others according to the investigator's judgment or as indicated by an answer of "yes" to the question 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) at the Screening Visit within the last six months on the lifetime version of C-SSRS.
• Based on investigators judgment the patient has a medical or neurological disorder or treatment for such disorder that could interfere with the study treatment or impair treatment compliance.
• The patient has had past episodes of extrapyramidal symptoms (EPS) under current medication within the last 3 month
• The patient takes other medication than those listed as allowed concomitant medication in Appendix III
• The patient is occupationally exposed to significant levels of ionizing radiation.

Sponsors & Collaborators

• H. Lundbeck A/S: lead

Study Sites (1)

US802

Rockville, Maryland, 20850, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Lu AF35700

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Limitations and Caveats

An estimate of the confidence interval for the parameter Emax in the dopamine D2 receptor occupancy model was not calculable.

Results Point of Contact

• Title: Email contact via
• Organization: H. LUndbeck A/S

LundbeckClinicalTrials@Lundbeck.com

+4536301311

Study Officials

• Email contact via H. Lundbeck

  LundbeckClinicalTrials@lundbeck.com

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2015
• First Posted: January 7, 2015
• Study Start: December 30, 2014
• Primary Completion: February 11, 2016
• Study Completion: February 11, 2016
• Last Updated: May 12, 2020
• Results First Posted: May 12, 2020

Record last verified: 2020-05

Locations

US (1)