Antipsychotic Agents, Central Nervous System Depressants, Mental Disorders, Molecular Mechanisms of Pharmacological Action, Mood Disorders, Neurotransmitter Agents, Physiological Effects of Drugs, Psychotic Disorders, Psychotropic Drugs, Schizophrenia, Schizophrenia Spectrum, Tranquilizing Agents
Conditions
Keywords
Schizophrenia, Paliperidone Palmitate, Serotonin 5-HT2 Receptor Antagonists, Serotonin Antagonists, Serotonin Agents, Dopamine D2 Receptor Antagonists, Dopamine Antagonists, Dopamine Agents
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.
Detailed description
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. On the day before the last dosing day visit (Day 140 for LY03010 treatment group and Day 147 for SUSTENNA treatment group), subjects will come to the clinical facility and stay at sites for 8 days for PK collection and other assigned activities. The schedules of assessments for each treatment group are listed in Table 2 and Table 3. 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.
Interventions
DRUGLY03010; paliperidone palmitate
LY03010 is white to off-white sterile aqueous extended-release suspension of paliperidone palmitate for IM injection.
DRUGINVEGA SUSTENNA
INVEGA SUSTENNA (234 mg, 156 mg) is manufactured by Janssen Pharmaceuticals, Inc and is commercially available.
Sponsors
Luye Pharma Group Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
To participate in the study, patients must meet all inclusion criteria at screening: 1. Capable of giving informed consent and complying with study procedures. 2. 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. 3. Have a stable place of residence for the 3 months prior to screening and throughout the study. 4. 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. 5. 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. 6. 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. 7. Clinical Global Impression-Severity (CGI-S) score of 1 to 4, inclusive. 8. 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. 9. Body mass index (BMI) ≥17.0 and ≤ 37 kg/m2; body weight ≥ 50 kg. 10. 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. 11. 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.
Exclusion criteria
Patients will be excluded from study entry if 1 or more
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The relative bioavailability of LY03010 versus INVEGA SUSTENNA at steady-state | 176 days | 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. |
| Relative Bioavailability of LY03010 compared to Listed Drug | 176 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare the PK profile between LY03010 and INVEGA SUSTENNA at the initial phase | 36 days | AUC of paliperidone from the two different initial dosing regimens will be compared. |
| Compare the PK profile between the two treatments at the initial phase. | 36 days | Cmax of paliperidone from the two different initial dosing regimens will be compared. |
| Compare the PK profile between the two treatments. | 36 days | Cmin of paliperidone from the two different initial dosing regimens will be compared. |
Countries
United States
Outcome results
None listed