A Multiple Dose Study to Assess the Safety, Tolerability and PK of Risperidone Extended Release Capsules

NCT04567524 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LYN-005-C-004
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 5

Brief Summary

Lyndra is developing an oral, extended release (ER) formulation of risperidone (LYN-005) presented in a capsule dosage form with the intent of reducing the frequency of dosing orally-administered medications to once weekly or less and thereby improving the management of schizophrenia. Study LYN-005-C-004 will evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple dose administration of the ER formulation at two dose levels of LYN-005 relative to IR risperidone.

Conditions

Schizophrenia Schizoaffective

Outcome Measures

Primary Outcomes (5)

• Participants With at Least One Treatment Emergent Adverse Event (TEAE).

  Incidence of treatment emergent adverse events (TEAEs) reported as participants with at least one treatment emergent adverse event (TEAE).

  35 days

• Total Number of Treatment Emergent Adverse Events (TEAEs).

  Incidence of treatment emergent adverse events (TEAEs) reported as total number of TEAEs.

  35 days

• Active Moiety PK (Cmax)

  Active moiety Cmax (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 Extended Release (ER) capsules relative to Immediate Release (IR) risperidone tablets at 2 dose levels.

  Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.

• Active Moiety PK (AUC0-24, AUC0-168)

  Active moiety AUC (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 ER capsules relative to IR risperidone tablets at 2 dose levels.

  Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.

• Active Moiety Tmax

  Active Moiety Tmax (h) (risperidone and 9-hydroxyrisperidone combined) after repeat weekly doses of LYN-005 ER capsules relative to IR risperidone tablets at 2 dose levels.

  Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.

Secondary Outcomes (4)

• PK of Risperidone (Cmax).

  Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.

• PK of Risperidone (AUC0-24h, AUC0-168).

  Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.

• PK of 9-Hydroxyrisperidone (Cmax).

  Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.

• PK of 9-Hydroxyrisperidone (AUC0-24h, AUC0-168h).

  Reported data was obtained following multiple dose administration of 3 weekly doses [(IR, Day-1), (ER, Week 1), ER Week 3)] of 14 or 28 mg risperidone LYN-005 capsules to assess extended release PK.

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

LYN-005: capsules containing LYN-005 stellate; the 14mg dose of LYN-005 contains 3 active arms containing risperidone, and 3 inactive arms and the 28 mg dose of LYN-005 contains 6 active arms containing risperidone. AND IR Risperidone Matched Placebo: Orange capsule-shaped tablets containing inactive ingredient.

Drug: LYN-005

Arm 2

PLACEBO COMPARATOR

LYN-005 Matched Placebo: Size 00EL capsules containing inactive ingredient with no stellate. AND IR Risperidone: Risperidone 2 mg (orange) capsule-shaped tablets.

Drug: LYN-005

Interventions

LYN-005 DRUG

LYN-005 (14 or 28 mg weekly) plus IR risperidone matched placebo.

Also known as: Risperidone

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female aged ≥18 and ≤50 years.
• Current diagnosis of schizophrenia or schizoaffective disorder according to DSM-5 criteria as confirmed by the MINI 7.0.2.
• The following psychiatric criteria were used to determine subject eligibility:
• Duration of diagnosis of schizophrenia or schizoaffective disorder of ≥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 an oral antipsychotic medication (single agent) 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 prior to the Screening visit and for the duration of the study.
• CGI-S score of ≤4 (moderately ill).
• PANSS score of ≤80 points.
• Body mass index (BMI) of ≥18 kg/m2 and ≤35 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.
• Subject has identified a caregiver or personal contact with whom the subject communicates with at least once a week.

You may not qualify if:

• Subjects 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 subjects with high risk of stricture, e.g., Crohn's disease.
• Diagnosis of a condition known to elevate or lower gastric pH, e.g., achlorhydria or hypochlorhydria.
• Prior varices or small or large bowel obstructions.
• Prior abdominal or upper gastrointestinal surgery (prior uncomplicated laparoscopic procedures including appendectomy or colectomy).
• History of dysphagia or aspiration in the last 5 years.
• History of an esophageal motility disorder or undergoing treatment for a gastric motility disorder.
• Significant history of diarrhea or constipation within 3 months of Screening
• Multiple episodes of abdominal pain within 3 months of Screening.
• Subjects who experience moderate or severe dysmenorrhea or menorrhagia (with use of pain medication) 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. The ARSS scale is as follows:
• None = 0 no symptoms Mild = 1 awareness of symptom, but easily tolerated Moderate = 2 discomfort sufficient to cause interference with normal activities Severe = 3 incapacitating, with inability to perform normal activities.
• Subjects with PILL-5 questionnaire score of 5 or greater.
• Medical history or current diagnoses indicating the presence of any of the below conditions:
• Presence of an uncontrolled, unstable, clinically significant medical condition could that could put the subject at risk because of participation in the study, interfere with the subject's ability to participate in the study or influence the interpretation of safety or PK evaluations.

Sponsors & Collaborators

• Lyndra Inc.: lead
• Worldwide Clinical Trials: collaborator

Study Sites (5)

Collaborative Neuroscience Research, LLC

Long Beach, California, 90806, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

Community Clinical Research, Inc

Austin, Texas, 78754, United States

Location

Pillar Clinical Research, LLC

Richardson, Texas, 75080, United States

Location

MeSH Terms

Conditions

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

Results Point of Contact

• Title: Nayana Nagaraj, Senior Medical Director
• Organization: Lyndra Therapeutics

Nnagaraj@lyndra.com

3023040091

Study Officials

• Richard Scranton, MD, MPH

  Chief Medical Officer

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Although treatment assignment was blinded; the dose level was not blinded. The dose of LYN-005 (14 or 28 mg)/IR risperidone (2 or 4 mg/day) administered was based on the subject's current antipsychotic medication dose. Randomization was stratified by risperidone dose (LYN-005 14 mg/IR risperidone 2 mg/day \[low dose\] and LYN-005 28 mg/IR risperidone 4 mg/day \[high dose\], with a maximum of 16 subjects enrolled in each stratum. Within each stratum, subjects were randomized on a 3:1 basis to either LYN-005 or risperidone, respectively.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: LYN-005-C-004 was a blinded, multiple-dose, randomized, parallel group, safety, tolerability and PK study of LYN-005 in subjects with a primary diagnosis of schizophrenia or schizoaffective disorder in general good health. Eligible subjects were clinically stable and receiving a therapeutic dose of an approved oral antipsychotic drug for a minimum of 6 weeks at the time of Screening. Enrolled subjects were evaluated under steady-state conditions on commercially-available IR risperidone tablets and then assigned in blinded fashion either to LYN-005 weekly or continued encapsulated IR risperidone daily for 3 weeks to attain (or continue) steady-state exposure.

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: September 28, 2020
• Study Start: August 13, 2020
• Primary Completion: December 22, 2020
• Study Completion: December 22, 2020
• Last Updated: February 8, 2023
• Results First Posted: February 8, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)