Relative Bioavailability of LY03010 Compared to Listed Drug

NCT04922593 | Completed Phase 1 FDA Drug

• 1 other identifier: LY03010/CT-USA-103
• Study Type: interventional
• Target: 281
• Locations: 1 country
• Sites: 9

Brief Summary

This is a randomized, multiple-dose, open-label, parallel-group study. Subjects will undergo screening evaluations to determine eligibility within 28 days prior to study drug administration. Approximately 280 eligible subjects will be randomized in a 1:1 ratio into 1 of 2 treatment groups. Subjects will be admitted to the clinical facilities the day before dosing (Day 0), and will be randomized and receive the first dosing on Day 1. Subjects will stay at site till Day 2 after PK collection. All subjects will return to the clinical sites at designated study days for dosing, PK sample collections and assigned clinical activities. All subjects randomized to LY03010 treatment group will receive the first dose of 351 mg LY03010 by IM injection on Day 1 in the deltoid muscle, followed by five (5) monthly dosing of 156 mg LY03010 in the gluteal muscle with the last dose on Day 141. All subjects randomized to SUSTENNA treatment group will receive the first dose of 234 mg SUSTENNA by IM injection on Day 1 in the deltoid muscle, and a second IM dose of 156 mg SUSTENNA on Day 8 in the deltoid muscle, followed by five (5) monthly IM dosing of 156 mg of SUSTENNA in the gluteal muscle with the last dose on Day 148. End of Study (EOS) visit for LY03010 treatment group will be on Day 169, 28 days after last dosing day; End of Study for SUSTENNA treatment group will be on Day 176, 28 days after last dosing. At EOS visit, subjects will complete the study after a series of assigned clinical assessments. A 30-day follow up call will be conducted by the clinical research staff to ensure participant's well-being.

Conditions

Schizophrenia; Psychotic Disorders; Mood Disorders; Schizophrenia Spectrum; Mental Disorders; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Psychotropic Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action

Keywords

Schizophrenia; Paliperidone Palmitate; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Serotonin Agents; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Dopamine Agents

Outcome Measures

Primary Outcomes (2)

• The relative bioavailability of LY03010 versus INVEGA SUSTENNA at steady-state

  The relative bioavailability of LY03010 versus INVEGA SUSTENNA will be evaluated by the analysis of the area under the plasma concentration-time curve over a dosing interval at steady state (AUCtau-ss) of plasma paliperidone.

  176 days

• Relative Bioavailability of LY03010 compared to Listed Drug

  The relative bioavailability of LY03010 versus INVEGA SUSTENNA will be evaluated by the analysis of maximum peak steady-state (Cmax-ss) of plasma paliperidone concentration during a dosage interval.

  176 days

Secondary Outcomes (3)

• Compare the PK profile between LY03010 and INVEGA SUSTENNA at the initial phase

  36 days

• Compare the PK profile between the two treatments at the initial phase.

  36 days

• Compare the PK profile between the two treatments.

  36 days

Study Arms (2)

LY03010 treatment group

EXPERIMENTAL

LY03010 (paliperidone palmitate) is a pharmaceutical equivalent drug product to the listed drug (LD) product INVEGA SUSTENNA. The chemical name is (±)-3-\[2-\[4-(6-fluoro-1,2-benzisoxazol-3yl)piperidinyl\]ethyl\]-6,7,8,9-tetrahydro-2-methyl-4oxo-4Hpyrido\[1,2-a\]pyrimidin-9-yl hexadecanoate. Its molecular formula is C39H57FN4O4 and its molecular weight is 664.89 g/mol. LY03010 is white to off-white sterile aqueous extended-release suspension of paliperidone palmitate for IM injection. In LY03010 treatment group, all subjects will receive the first dose of 351 mg IM injection on Day 1 in the deltoid muscle, followed by five (5) monthly dosing of 156 mg IM injection in the gluteal muscle with the last dose on Day 141.

Drug: LY03010; paliperidone palmitate

INVEGA SUSTENNA treatment group

ACTIVE COMPARATOR

INVEGA SUSTENNA (234 mg, 156 mg) is manufactured by Janssen Pharmaceuticals, Inc and is commercially available. INVEGA SUSTENNA is provided in a prefilled syringe (cyclic-olefin-copolymer) with a plunger stopper and tip cap (bromobutyl rubber). In SUSTENNA treatment group, all subjects will receive the first dose of 234 mg IM injection in the deltoid muscle on Day 1, and a second dose of 156 mg of IM injection in the deltoid muscle on Day 8, followed by five (5) monthly dosing of 156 mg IM injection in the gluteal muscle with the last dose on Day 148.

Drug: INVEGA SUSTENNA

Interventions

LY03010; paliperidone palmitate DRUG

LY03010 is white to off-white sterile aqueous extended-release suspension of paliperidone palmitate for IM injection.

LY03010 treatment group

INVEGA SUSTENNA DRUG

INVEGA SUSTENNA (234 mg, 156 mg) is manufactured by Janssen Pharmaceuticals, Inc and is commercially available.

INVEGA SUSTENNA treatment group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving informed consent and complying with study procedures.
• Have an identified support person (e.g., family member, case worker, social worker) who is considered reliable by the Investigator to help ensure compliance with study visits and to alert staff of any issues of concern.
• Have a stable place of residence for the 3 months prior to screening and throughout the study.
• Male or female ≥18 to ≤65 years of age who meets diagnostic criteria for schizophrenia or schizoaffective disorder according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) for at least 1 year before screening.
• Be on a stable dose of oral antipsychotic medication(s) other than risperidone, paliperidone, clozapine, ziprasidone, or thioridazine for at least 4 weeks prior to screening.
• Be clinically stable based on clinical assessments and a Positive and Negative Syndrome Scale (PANSS) total score ≤75 as well as a PANSS HATE (hostility, anxiety, tension and excitement) subtotal score \<16 at screening.
• Clinical Global Impression-Severity (CGI-S) score of 1 to 4, inclusive.
• For patients with schizoaffective disorder only: Young Mania Rating Scale (YMRS) ≤12 and Hamilton Rating Scale for Depression, 21-item version (HAM-D-21) ≤12.
• Body mass index (BMI) ≥17.0 and ≤ 37 kg/m2; body weight ≥ 50 kg.
• All female patients (childbearing potential and non-childbearing potential) must have a negative pregnancy test result at both screening and baseline. Female patients must meet 1 of the following 3 conditions: (i) postmenopausal for at least 12 months without an alternative medical cause, (ii) surgically sterile (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal occlusion) based on patient report, or (iii) if of childbearing potential (WOCBP) and heterosexually active, practicing or agree to practice a highly effective contraception method of birth control. Highly effective methods of birth control include an intrauterine device (IUD), intrauterine hormone-releasing system (IUS), and contraceptives (oral, skin patches, or implanted or injectable products) using combined or progestogen-only hormonal contraception associated with inhibition of ovulation. A vasectomized male partner is an acceptable birth control method if the vasectomized partner is the sole sexual partner of the female patient and the vasectomized partner has received medical confirmation of surgical success. Highly effective methods of birth control must be used for at least 14 days prior to study drug dosing, throughout the study, and for at least 200 days after the end-of-study (EOS) visit to minimize the risk of pregnancy.
• Sexually active fertile male patients must be willing to use acceptable contraception methods (such as double barrier methods of a combination of male condom with either cap, diaphragm or sponge with spermicide) from study drug dosing, throughout the study, and for at least 200 days after the EOS visit if their partners are women of childbearing potential.

You may not qualify if:

• Primary and active DSM-V Axis I diagnosis other than schizophrenia or schizoaffective disorder.
• Patients who meet DSM-V criteria for substance abuse (moderate or severe), or test positive for a drug of abuse or alcohol at screening or baseline with the exception of 1) caffeine or nicotine in the past 6 months prior to screening, or 2) test positive for barbiturate or benzodiazepine which can be accounted for by documented prescriptions from a treating physician as a part of the treatment for the patient's psychiatric illness.
• Patients who received any of following treatment:
• Use of oral risperidone or paliperidone within 2 weeks before screening.
• Use of Clozapine, Thioridazine or Ziprasidone within 4 weeks before screening.
• Use of 2-week depot formulation of risperidone (RISPERDAL CONSTA) within 3 months, 1-month depot formulation of risperidone (PERSERIS KIT) or 9-hydroxy risperidone (INVEGA SUSTENNA) within 1 year, or 3-month depot formulation of 9-hydroxy risperidone (INVEGA TRINZA) within 2 years before screening. Use of other long-acting injectable for the treatment of schizophrenia within 4 weeks before screening.
• Use of nonselective or irreversible monoamine oxidase inhibitor (MAOI) antidepressants within 30 days before screening. Patients on other antidepressants should be excluded as well unless the dose has been stable for more than 30 days before screening.
• Use of strong inducers or inhibitors of CYP3A4 or P-glycoprotein (P-gp) within 2 weeks or 5 half lives, whichever is longer, before screening.
• Electroconvulsive therapy within 60 days before screening.
• Known or suspected hypersensitivity or intolerance of risperidone, paliperidone, or any of their excipients (oral risperidone tolerability test will be completed during the screening period, approximately14 days but no less than 9 days prior to dosing, for patients without documented evidence \[medical record or written statement from a licensed medical practitioner who has treated the patient\] of tolerating risperidone or paliperidone, and patients who show an allergic reaction to this test will be excluded from the study).
• Patients who pose a significant risk of a suicide attempt based on history or the Investigator's judgment; answer "yes" to Suicidal Ideation items 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) for current or past 6 months on the "Baseline/Screening version" at screening; have had suicidal behavior in the last 6 months as measured by the C-SSRS at screening; or are at imminent risk of suicide or violent behavior based on the Investigator's clinical assessment or the C-SSRS assessment of lifetime suicidal ideation or behavior at screening.
• Any one or more of the following 3 conditions: (i) clinically significant liver dysfunction, (ii) hepatitis B surface antigen (HBsAg) positive, hepatitis C (HCV) positive, or (iii) a serum alanine transaminase (ALT) or aspartate transaminase (AST) \> 2x upper limit of normal (ULN) range; or a total bilirubin \> 1.5 x ULN(if the ALT or AST levels are between 2x and 3x ULN in the first screening test and the elevation may be caused by non-specific reasons in the judgment of the Investigator, a second test can be performed after one week. If the repeated ALT or AST levels are still \>2x ULN, the patient must be excluded from the study. Patients who are HCV antibody reactive but confirmed HCV RNA not detected may be enrolled, if this condition has been previously considered stable without treatment or after the completion of appropriate treatment, and liver function is normal.
• History of symptomatic orthostatic hypotension or with a decrease of ≥ 20 mmHg in systolic blood pressure (SBP) or decrease of ≥10 mmHg in diastolic blood pressure (DBP) when changing from supine to standing position after having been in the supine position for at least 5 minutes or SBP less than 105 mmHg in a supine position prior to randomization.
• Uncontrolled diabetes or hemoglobin A1c (HbAlc) level ≥ 7% at screening.
• Indication of impaired renal function at Screening (estimated glomerular filtration rate \< 80 mL/min).

Sponsors & Collaborators

• Luye Pharma Group Ltd.: lead

Study Sites (9)

Collaborative Neuroscience Network, Inc.

Garden Grove, California, 92845, United States

Location

Synergy San Diego

Lemon Grove, California, 91945, United States

Location

CNS Network, LLC

Torrance, California, 90502, United States

Location

Innovative Clinical Research, Inc.

Miami Lakes, Florida, 33016, United States

Location

Uptown Research Institute, LLC

Chicago, Illinois, 60640, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

InSite Clinical Research, LLC

DeSoto, Texas, 75115, United States

Location

Pillar Clinical Research, LLC

Richardson, Texas, 75080, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Mood Disorders; Mental Disorders

Interventions

Paliperidone Palmitate

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Rui Li, MD

  Luye Pharma US Ltd

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: April 27, 2021
• First Posted: June 10, 2021
• Study Start: January 13, 2021
• Primary Completion: March 15, 2022
• Study Completion: April 15, 2022
• Last Updated: April 25, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)