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

NCT ID: NCT04567524

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-13
• Study Completion Date: 2020-12-22

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.

Detailed Description

LYN-005-C-004 is 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 must be 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 will be 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.

Conditions

Schizophrenia Schizoaffective

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1

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.

Group Type: ACTIVE_COMPARATOR

LYN-005

Intervention Type: DRUG

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

Arm 2

LYN-005 Matched Placebo: Size 00EL capsules containing inactive ingredient with no stellate.

AND

IR Risperidone: Risperidone 2 mg (orange) capsule-shaped tablets.

Group Type: PLACEBO_COMPARATOR

LYN-005

Intervention Type: DRUG

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

Interventions

LYN-005

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

Intervention Type: DRUG

Other Intervention Names

Risperidone

Eligibility Criteria

Inclusion Criteria

1. Male or female aged ≥18 and ≤50 years.

2. Current diagnosis of schizophrenia or schizoaffective disorder according to DSM-5 criteria as confirmed by the MINI 7.0.2.

3. The following psychiatric criteria were used to determine subject eligibility:

1. Duration of diagnosis of schizophrenia or schizoaffective disorder of ≥2 years.

2. Outpatient; not hospitalized for worsening of schizophrenia within the last 6 months (partial hospitalization for social management within this time period is acceptable).

3. Medically stable over the last month and psychiatrically stable without significant symptom exacerbation over the last 3 months.

4. Stabilized on an oral antipsychotic medication (single agent) for a minimum of 6 weeks at the time of Screening.

5. 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.

6. CGI-S score of ≤4 (moderately ill).

7. PANSS score of ≤80 points.

8. Body mass index (BMI) of ≥18 kg/m2 and ≤35 kg/m2.

9. Able to read and understand study procedures and provide written informed consent before the initiation of any protocol-specific procedures.

10. Willing to comply with all protocol-specified procedures and availability for the duration of the study.

11. Subject has identified a caregiver or personal contact with whom the subject communicates with at least once a week.

Exclusion Criteria

1. Subjects with known clinically significant esophageal or GI disease, including but not limited to:

1. Known strictures such as esophageal web, pyloric stenosis, or small intestinal stricture, or subjects with high risk of stricture, e.g., Crohn's disease.

2. Diagnosis of a condition known to elevate or lower gastric pH, e.g., achlorhydria or hypochlorhydria.

3. Prior varices or small or large bowel obstructions.

4. Prior abdominal or upper gastrointestinal surgery (prior uncomplicated laparoscopic procedures including appendectomy or colectomy).

5. History of dysphagia or aspiration in the last 5 years.

6. History of an esophageal motility disorder or undergoing treatment for a gastric motility disorder.

7. Significant history of diarrhea or constipation within 3 months of Screening

8. Multiple episodes of abdominal pain within 3 months of Screening.

9. Subjects who experience moderate or severe dysmenorrhea or menorrhagia (with use of pain medication) within 3 months of Screening.

10. 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.

2. Subjects with PILL-5 questionnaire score of 5 or greater.

3. Medical history or current diagnoses indicating the presence of any of the below conditions:

1. 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.

2. 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 with 6 months of Screening.

3. Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of Screening.

4. Known immunocompromised status, including individuals who have undergone organ transplantation, on immunosuppression for an immunemediated disease, or are positive for human immunodeficiency virus (HIV).

5. Subjects with a positive test for active hepatitis B or C at Screening. Subjects 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.

6. Subjects who have donated more than 250 mL of blood within 30 days of Screening.

7. Subjects who have difficulties with venipuncture/cannulation, including difficulty accessing veins for blood sampling and/or history of coagulopathy or endocarditis.

8. Subjects with a current DSM-5 diagnosis of major depressive episode, panic disorder, agoraphobia, social anxiety disorder, obsessive- compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder on the MINI 7.0.2 or in the judgment of the Investigator. (Note that individuals with depression secondary to schizoaffective disorder are eligible).

9. Suicidal ideation associated with actual intent and a method or plan in the past 6 months, as measured by the C-SSRS (i.e., "Yes" answers on items 4 or 5) at Screening or having made a suicide attempt within the last 2 years.

10. Known or suspected (non-febrile) seizure disorder.

11. History of neuroleptic malignant syndrome.

12. Current or history of clinically significant tardive dyskinesia.

13. Known or suspected diagnosis of intellectual disability or organic brain disorder or other diagnosis that is primarily responsible for current symptoms and functional impairment.

14. Medically non-adherent in the management of their schizophrenia/schizoaffective disorder.

4. Use of the below medications/treatments in the 2 weeks before enrollment, including:

1. Proton pump inhibitors or H2 blockers.

2. Prokinetic agents.

3. Medications that may interfere with the absorption, metabolism, or excretion of risperidone, e.g.:

Drugs metabolized via CYP3A4 pathway, such as macrolide antibiotics and azole antifungals). Moderate or strong CYP3A4 p-glycoprotein (P-gp) enzyme inducers and inhibitors (carbamazepine, phenytoin, rifampicin, phenobarbital, itraconazole, verapamil). Moderate or strong CYP2D6 inhibitors (e.g., fluoxetine, fluoxetine combinations, paroxetine), or quinidine.

4. Concomitant medications, natural remedies, supplements or vitamins which are associated with changes to gastric motility or pH. Use of antacids is permissible, except within 2 hours of dosing with LYN-005.

5. Benzodiazepines; except lorazepam, diazepam and oxazepam, which are acceptable if for the treatment of depression, anxiety or insomnia.

6. Use of more than one antidepressant; or if on just one, a change in dose within 6 weeks of Screening.

7. Depot antipsychotic use within 9 months of Screening.

8. Electroconvulsive therapy within 3 months of Screening.

5. Subjects with clinically significant abnormal safety (e.g. physical examination, vital sign) or safety laboratory assessments, specifically:

1. Presence of a clinically significant abnormal laboratory result on blood or urine safety tests at Screening.

2. Anemia (hemoglobin below lower limit of normal reference range) at Screening.

3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥3.0 × upper limit of normal (ULN), or total bilirubin ≥1.5 × ULN.

4. Moderate or severe renal insufficiency at Screening (glomerular filtration rate <60 mL/min, as determined using the Cockcroft-Gault formula).

5. Heart rate of <50 beats per minute (bpm) at Screening.

6. Systolic blood pressure ≤100 or ≥150 and/or diastolic blood pressure ≤60 mmgHg or ≥100 mmHg at Screening.

7. HbA1c ≥6.5% at Screening.

8. Positive fecal occult blood test at Screening

9. Clinically significant prolactin elevation (≥200 ng/mL for females; ≥100 ng/mL for males).

6. Subjects with the below specified patterns of substance use at Screening:

1. Fulfillment of the DSM-5 criteria for moderate or severe substance use disorder (excluding nicotine and caffeine) within 6 months of Screening.

2. History of alcohol consumption exceeding moderate use; in males exceeding 21 units per week and in females exceeding 14 units per week (1 unit = 360 ml beer, 25 mL of 40% spirit or a 125 mL glass of wine) over the past month. Subjects are not permitted to consume alcohol during the inpatient stay nor 12 hours before any clinic visit while outpatient.

3. Positive ethanol breathalyzer.

4. Positive urine drug screen for substances of abuse other than cannabis.

5. Heavy nicotine use (consumption of >40 cigarettes or >36 mg of nicotine from other sources [e.g., vaping products] daily) or daily use of smokeless tobacco.

7. Subjects of reproductive potential who are (hetero) sexually active but unwilling to use acceptable means of contraception through the EOS. For clarity, subjects who are at least 1 year post-menopausal are not of reproductive potential. Acceptable means of contraception include:

1. Subjects who have been surgically sterilized.

2. Females of reproductive potential: diaphragm, injectable, oral/patch contraceptives for a minimum of 6 weeks, contraceptive sponge, implant, or intrauterine device in use prior to enrollment.

3. Males: condom in combination with any of the above means of contraception.

4. All subjects: abstinence may be an acceptable means of contraception as long as the individual consents to initiate immediate use of double barrier protection for the duration of the study should (hetero) sexual intercourse occur.

8. Subjects who are nursing or who have positive or indeterminate pregnancy tests at either Screening (serum test) or enrollment (urine test).

9. Use of any experimental agent within 1 month or 5 half-lives of Screening, whichever is longer.

10. Subjects who are employees or immediate family members of employees of the site, Sponsor or study-related vendors.

11. History of a serious allergic or hypersensitivity reaction to risperidone or LYN-005 excipients (refer to Investigator's Brochure).

12. Subjects with history of X-ray, computed tomography (CT) scan or angiogram of the abdomen within one year of Screening.

13. Subjects with CYP2D6 poor or underdetermined metabolizer status based on genetic testing.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Worldwide Clinical Trials

OTHER

Sponsor Role: collaborator

Lyndra Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Scranton, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Chief Medical Officer

Locations

Collaborative Neuroscience Research, LLC

Long Beach, California, United States

Atlanta Center for Medical Research

Atlanta, Georgia, United States

Hassman Research Institute

Marlton, New Jersey, United States

Community Clinical Research, Inc

Austin, Texas, United States

Pillar Clinical Research, LLC

Richardson, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

LYN-005-C-004

Identifier Type: -

Identifier Source: org_study_id