Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant

Study Overview
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Brief Summary
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This is an Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching from Oral Risperidone to Risperidone Implant (DLP-114).

Detailed Description
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Phase 1 open-label study in stable schizophrenia patients designed to evaluate the safety, tolerability, and PK of switching from 2 mg/day or 3 mg/day oral risperidone to two DLP-114 devices for a six or twelve-month dosing period.

Official Title
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Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant (DLP-114)

Conditions
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Schizophrenia

Intervention / Treatment
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* Combination Product: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients 18-70 years of age of both sexes diagnosed with schizophrenia or schizoaffective disorder according to DSM-V who have been stable on oral risperidone (2mg-3mg) for at least 2 weeks. Patient (and/or a patient's authorized legal representative) has provided written informed consent Patient meets the following criteria: Outpatient status PANSS Total Score ≤ 80 at screening. A score of ≤ 4 on the following PANSS items: i. Conceptual disorganization ii. Suspiciousness iii. Hallucinatory behavior iv. Unusual thought content v. Hostility d. CGI-I-S ≤ 4 (moderately ill)\Lack of clinically significant suicidal ideation or behavior; C-SSRS score type of 4-5 require evaluation by mental health professional to ensure patient safety in study Body Mass Index (BMI) within the range of 18.5 to 40.0 kg/m2 (inclusive); Ability to understand the nature and objectives of the trial, including risks and adverse events, and be able to read, review and sign the informed consent document prior to conduct of any study procedures; Willing and able to comply with the requirements of the study protocol; including willingness to visit the clinical facility for all outpatient visits and confinement periods; Have suitable venous access for blood sampling. Patient is assessed by the Investigator to be symptomatically stable with regard to pre-existing medical conditions as evidenced by medical history, non-clinically significant findings on physical examination, vital signs, clinical laboratory evaluations (hematology, serum chemistries, and urinalysis) or 12-lead electrocardiogram (ECG). Subjects may continue on their current prescribed medication regimens to control pre-existing medical and psychiatric conditions (other than schizophrenia) including the use of prescribed PRN medications. Exclusion Criteria: PANSS score at baseline is ≥ 20% change from screening. Hospitalized or required acute crisis intervention for symptom exacerbation in the 60 days prior to admission as determined by the Investigator Patient has a history of suicide attempt in the last year, or in the opinion of the investigator is currently at imminent risk of suicide. Patient experiencing acute depressive symptoms within the past 30 days, according to the Investigator's opinion, that required treatment with an antidepressant Has a current or recent (within 12 months) DSM-V diagnosis of moderate or severe substance use disorder (except for tobacco use disorder) or has a positive urine drug screen for prohibited substances at screening. Have impaired hepatic (ALT/AST >1.5 times higher than the upper limit of normal) or renal function (eGFR<50 mL/min) Previously defined hypersensitivity to Risperidone History of neuroleptic malignant syndrome (NMS) Electroconvulsive therapy within 6 months of admission Requires current use of agents that are strong inhibitors and inducers of cytochrome P450; Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the amide type (local anesthetic used during implant and explant procedures); Presence of clinically significant skin disorders (such as, but not limited to, skin cancer, psoriasis, eczema, or atopic dermatitis), evidence of recent sunburn, scar tissue, tattoo, open sore, body piercing or branding at the intended implantation site that would interfere with the implantation procedure or interfere with implant site assessments as determined by the investigator; History of clinically significant hypersensitivity or allergic reactions; Known allergy or hypersensitivity to PABA; Known allergy or hypersensitivity to parabens, local anesthetics of the ester type, and sulfa drugs including antibiotics and thiazide diuretics; Known hypersensitivity to titanium, implant materials or procedure; Administration of an investigational drug or device within 1 month prior to first dosing; Positive result for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody, or HIV antibody; Pregnant or lactating patients. Positive pregnancy test; Positive drug test for Methamphetamines, Opiates, Cocaine, Phencyclidine, Benzodiazepines, Barbiturates, Methadone, Antidepressants and Amphetamines or positive alcohol test at screening or prior to first dose; Poor CYP2D6 metabolizer; History of skin picking or delusional parasitosis; Known history of abnormal scar formation or family history of keloid formation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DLP-114 alpha-4 (6-months)<br>2 360mg Risperidone Implants | Combination Product: Risperidone<br>* Risperidone Implant<br>* Other names: DLP-114;|
| Experimental: DLP-114 alpha-7 (12-months)<br>2 435mg Risperidone Implants | Combination Product: Risperidone<br>* Risperidone Implant<br>* Other names: DLP-114;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Determine the number and percent of patients experiencing a treatment-emergent adverse event; | 6-12 months | 
| Local Tolerance | Evaluate the incidence of local site reactions | 6-12 months | 
| Tolerability of Implantation and Explantation Procedures | Assess the incidence of local site reactions and/or Adverse Events (AEs) reported during the implantation and explantation procedures | 6-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oral Pharmacokinetic (PK) Profile | Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety (risperidone + 9 OH risperidone) following repeated oral administrations | 24 hours | 
| Implant Pharmacokinetic (PK) Profile | Measure the plasma concentration of risperidone and 9-OH risperidone and active moiety (risperidone + 9 OH risperidone) following switch from oral risperidone to subcutaneous implantation of two DLP-114 devices. | 6-12 Months | 
| Positive and Negative Syndrome Scale (PANSS) | Measure exploratory treatment outcomes using the 30-item Positive and Negative Syndrome Scale (PANSS). The PANSS provides a total score (sum of the scores of all 30 items) ranging from 30 to 210, higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. Scores for 3 subscales, that is, for positive subscale (sum of the scores of all 7 items) and negative subscale (sum of the scores of all 7 items) ranges from 7 (absent) to 49 (extreme psychopathology), and for the general psychopathology subscale (sum of the scores of all 16 items) score ranges from 16 (absent) to 112 (extreme psychopathology) | 6-12 Months | 
| Clinical Global Impression-Improvement (CGI-I) Scale | Measure exploratory treatment outcomes using the CGI-I scale. The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. | 6-12 Months | 
| Mass Balance | Measure the amount of risperidone drug substance remaining in the DLP-114 reservoir following its removal, in order to estimate average daily output and duration | 6-12 Months | 
| Implant device placement depth | Determine average depth of implant device placement measured by ultrasound in mm | 6-12 Months | 
| Determine potential implant migration | Migration measured by the distance between the incision and the proximal end of the implant device | 6-12 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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risperidone, schizophrenia, implant