A Study to Evaluate the Safety and Tolerability of Long-Acting Oral Risperidone (LYN-005) in Participants With Schizophrenia or Schizoaffective Disorder

NCT06878833 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: LYN-005-C-302
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Lyndra Therapeutics, Inc., is developing a long-acting oral (LAO) treatment of risperidone (LYN-005) in a capsule dosage form (LYNX® drug delivery platform). The intent of LYN-005 is to reduce the dosing frequency of orally-administered risperidone to once weekly or less and, thereby improve treatment adherence and management of schizophrenia and schizoaffective disorder. This study will evaluate the safety and tolerability of multiple administrations of LYN-005 at 3 dose levels.

Conditions

Schizophrenia; Schizoaffective Disorder

Keywords

Schizophrenia; Schizoaffective Disorder; Risperidone; LYN-005; long-acting oral (LAO) therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  OL Cohort: Screening through Day 57; DB Cohort: Screening through Day 203

Secondary Outcomes (4)

• PK Evaluation: Minimum Observed Concentration (Cmin) of Active Moiety at Week 5 (OL Cohort only)

  Week 5: postdose: 24 hours (±30 minutes), 48 hours (±30 minutes), 72 hours (±30 minutes), 96 hours (±30 minutes), 120 hours (±30 minutes),144 hours (±30 minutes), and 168 hours (up to 30 minutes before 168 hours)

• PK Evaluation: Maximal Observed Concentration (Cmax) of Active Moiety at Week 5 (OL Cohort only)

  Week 5: postdose: 24 hours (±30 minutes), 48 hours (±30 minutes), 72 hours (±30 minutes), 96 hours (±30 minutes), 120 hours (±30 minutes),144 hours (±30 minutes), and 168 hours (up to 30 minutes before 168 hours)

• PK Evaluation: Average Concentration (Cavg) of Active Moiety at Week 5 (OL Cohort only)

  Week 5: postdose: 24 hours (±30 minutes), 48 hours (±30 minutes), 72 hours (±30 minutes), 96 hours (±30 minutes), 120 hours (±30 minutes),144 hours (±30 minutes), and 168 hours (up to 30 minutes before 168 hours)

• Change in Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCI-PANSS) Over Time

  OL Cohort: Baseline, Day 22 and 43; DB Cohort: Baseline, Days 22, 43, 92, 106, 134, 162, 183

Study Arms (3)

Open Label (OL) Cohort

EXPERIMENTAL

After a 7-day run-in period in which participants receive immediate release (IR) risperidone (2 mg/day, 4 mg/day, or 6 mg/day, based on prior antipsychotic drug dose) and a single dose of LYN-005-matched placebo, participants receive weekly doses of 15, 30, or 45 mg of LYN-005 for 7 weeks.

Drug: LYN-005 (risperidone); Drug: Placebo for LYN-005; Drug: IR Risperidone

Double Blind (DB) Cohort: LYN-005

EXPERIMENTAL

After a 7-day run-in period in which participants receive IR risperidone (2 mg/day, 4 mg/day, or 6 mg/day, based on prior antipsychotic drug dose) and a single dose of LYN-005-matched placebo, participants receive weekly doses of 15, 30, or 45 mg of LYN-005 and daily doses of IR risperidone-matched placebo for 26 weeks.

Drug: LYN-005 (risperidone); Drug: Placebo for LYN-005; Drug: IR Risperidone; Drug: Placebo for IR Risperidone

Double Blind (DB) Cohort: IR Risperidone

ACTIVE COMPARATOR

After a 7-day run-in period in which participants receive IR risperidone (2 mg/day, 4 mg/day, or 6 mg/day, based on prior antipsychotic drug dose) and a single dose of LYN-005-matched placebo, participants receive daily doses of 2, 4, or 6 mg IR risperidone and weekly doses of LYN-005-matched placebo for 26 weeks.

Drug: Placebo for LYN-005; Drug: IR Risperidone; Drug: Placebo for IR Risperidone

Interventions

LYN-005 (risperidone) DRUG

long-acting oral (LAO) capsule

Double Blind (DB) Cohort: LYN-005; Open Label (OL) Cohort

Placebo for LYN-005 DRUG

capsule

Double Blind (DB) Cohort: IR Risperidone; Double Blind (DB) Cohort: LYN-005; Open Label (OL) Cohort

IR Risperidone DRUG

tablets

Double Blind (DB) Cohort: IR Risperidone; Double Blind (DB) Cohort: LYN-005; Open Label (OL) Cohort

Placebo for IR Risperidone DRUG

tablets

Double Blind (DB) Cohort: IR Risperidone; Double Blind (DB) Cohort: LYN-005

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 and ≤65 years.
• Current diagnosis of schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM-5) criteria as confirmed by the Mini International Neuropsychiatric Interview version 7.0.2 (MINI 7.0.2).
• Psychiatric criteria:
• Duration of diagnosis of schizophrenia or schizoaffective disorder for ≥2 years.
• Outpatient; not hospitalized for worsening of schizophrenia within the last 6 months (partial hospitalization for social management within this time period is acceptable).
• Medically stable over the last month and psychiatrically stable without significant symptom exacerbation over the last 3 months.
• Stabilized on a therapeutic dose of an oral antipsychotic drug for a minimum of 6 weeks at the time of Screening.
• On a stable dosage of all permitted non-antipsychotic medications (except for medication to be used on an as-needed basis) for at least 1 month before the Screening visit and for the duration of the study.
• Clinical Global Impression-Severity (CGI-S) score of ≤4 (moderately ill) at Screening and Day -7.
• Positive and Negative Syndrome Scale (PANSS) score of ≤80 points at Screening.
• Body mass index (BMI) of ≥18 kg/m2 and ≤38 kg/m2.
• Able to read and understand study procedures and provide written informed consent before the initiation of any protocol-specific procedures.
• Willing to comply with all protocol-specified procedures and availability for the duration of the study.

You may not qualify if:

• Participants with known clinically significant esophageal or GI disease, including but not limited to:
• Known strictures such as esophageal web, pyloric stenosis, or small intestinal stricture, or participants with high risk of stricture, e.g., Crohn's disease.
• Prior varices or small or large bowel obstructions.
• Prior abdominal or upper gastrointestinal surgery including gastric bypass or removal of a significant portion of the gastrointestinal (GI) tract that may impose a high risk of strictures (prior uncomplicated laparoscopic procedures including appendectomy or colectomy are permitted).
• History of diarrhea or constipation within 3 months of Screening that in the opinion of the investigator would be considered clinically significant.
• Multiple episodes of moderate or severe abdominal pain within 3 months of Screening.
• History of moderate to severe Acid Reflux Disease or a score of ≥2 on the Acid Reflux Severity Scale (ARSS) \[2\], indicating moderate to severe symptoms.
• PILL-5 questionnaire score of 5 or greater.
• Any clinically significant medical, surgical or psychiatric condition that in the opinion of the investigator would exclude them from the study, including:
• Presence of an uncontrolled, unstable, clinically significant medical condition that could put the participant at risk because of participation in the study, interfere with the participant's ability to participate in the study or influence the interpretation of safety or pharmacokinetic (PK) evaluations.
• History of a major cardiovascular event (myocardial infarction, cardiac surgery or revascularization, unstable angina, stroke, or transient ischemic attack) or a hospitalization for heart failure within 6 months of Screening.
• Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of Screening.
• Known immunocompromised status, including individuals who have undergone organ transplantation, on immunosuppression for an immune mediated disease, or are positive for human immunodeficiency virus (HIV).
• Positive test for active hepatitis B or C at Screening. Participants with successfully treated hepatitis B infection which has been resolved for greater than 1 year or successfully treated hepatitis C infection will not be excluded.
• Have donated more than 250 mL of blood within 30 days of Screening.

Sponsors & Collaborators

• Lyndra Inc.: lead

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nayana Nagaraj

  Lyndra Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 17, 2025
• Study Start: April 18, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share