Clinical trial NCT04418466: Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant
Official title: Open-Label Study in Stable Schizophrenia Patients to Evaluate the Safety, Tolerability, and Pharmacokinetics of Switching From Oral Risperidone to Risperidone Implant (DLP-114)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Schizophrenia
Keywords: risperidone
schizophrenia
implant
Lead sponsor: Delpor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2020-06-05
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: Phase 1 open-label study in stable schizophrenia patients designed to evaluate the safety, tolerability, and Pharmacokinetics 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.

Eligibility criteria: Inclusion Criteria:

1. Adult patients 18-70 years of age of both sexes diagnosed with schizophrenia or schizoaffective disorder according to Diagnostic and Statistical Manual (DSM)-V who have been stable on oral risperidone (2mg-3mg) for at least 2 weeks.
2. Patient (and/or a patient's authorized legal representative) has provided written informed consent
3. Patient meets the following criteria:

   1. Outpatient status
   2. PANSS Total Score ≤ 80 at screening.
   3. A score of ≤ 4 on the following PANSS items:

   i. Conceptual disorganization ii. Suspiciousness iii. Hallucinatory behavior iv. Unusual thought content v. Hostility d. Clinical Global Impression Scale (CGI-S) ≤ 4 (moderately ill)\\Lack of clinically significant suicidal ideation or behavior; Columbia Suicide Severity Rating Scale (C-SSRS) score type of 4-5 require evaluation by mental health professional to ensure patient safety in study
4. Body Mass Index (BMI) within the range of 18.5 to 40.0 kg/m2 (inclusive);
5. 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;
6. 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;
7. Have suitable venous access for blood sampling.
8. 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:

1. PANSS score at baseline is ≥ 20% change from screening.
2. Hospitalized or required acute crisis intervention for symptom exacerbation in the 60 days prior to admission as determined by the Investigator
3. 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.
4. Patient experiencing acute depressive symptoms within the past 30 days, according to the Investigator's opinion, that required treatment with an antidepressant
5. 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.
6. Have impaired hepatic (Alanine transaminase (ALT) /aspartate aminotransferase (AST) \>1.5 times higher than the upper limit of normal) or renal function (eGFR\<50 mL/min)
7. Previously defined hypersensitivity to Risperidone
8. History of neuroleptic malignant syndrome (NMS)
9. Electroconvulsive therapy within 6 months of admission
10. Requires current use of agents that are strong inhibitors and inducers of cytochrome P450;
11. Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the amide type (local anesthetic used during implant and explant procedures);
12. 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;
13. History of clinically significant hypersensitivity or allergic reactions;
14. Known allergy or hypersensitivity to para-aminobenzoic acid (PABA);
15. Known allergy or hypersensitivity to parabens, local anesthetics of the ester type, and sulfa drugs including antibiotics and thiazide diuretics;
16. Known hypersensitivity to titanium, implant materials or procedure;
17. Administration of an investigational drug or device within 1 month prior to first dosing;
18. Positive result for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody, or HIV antibody;
19. Pregnant or lactating patients. Positive pregnancy test;
20. 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;
21. Poor CYP2D6 metabolizer;
22. History of skin picking or delusional parasitosis;
23. Known history of abnormal scar formation or family history of keloid formation

Primary outcomes:
measure: Adverse Events
timeFrame: Up to 8 months and up to 15 months for groups 1 and 2 respectively.
measure: Percentage of Implant Site Assessments With a Dermal Irritation Scale Rating Greater Than Zero
timeFrame: 6 months and 12 months for groups 1 and 2 respectively.
measure: Number of Participants Who Experienced an AE Related to Implantation or Explantation Procedures
timeFrame: 6 months and 12 months for groups 1 and 2 respectively.
Secondary outcomes:
measure: Oral Phase Cave: Average Plasma Concentration of Active Moiety (Risperidone + 9 OH Risperidone) During 24 Hours After 3 Days of Repeated 3mg QD Oral Administrations
timeFrame: t=0, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours following oral administration.
measure: Implant Cave: Average Plasma Concentration of Active Moiety (Risperidone + 9 OH Risperidone) During the Implant Phase
timeFrame: PK blood draw & analysis were performed per protocol time intervals; 0, 1, 2, 3, 4, 6, 8, 12, 24, 28, 32, 36, 48, and 52 hours post-placement of implants; 1x/day for 4 additional days, 1x/week during days 5-28; biweekly until day of device removal.
measure: Average Positive and Negative Syndrome Scale (PANSS) During the Study (Oral & Implant Phases)
timeFrame: For group 1: Screening period, day -1, day 84, day 183; and for Group 2: Screening period, day -1, day 84, day 182, day 280, day 364.
measure: Average Clinical Global Impression-Improvement (CGI-I) Scale During the Implant Phase
timeFrame: CGI-I assessments were conducted over the course of the study per the protocol schedule of assessments. For Group 1: day 7, 14, 28, 42, 70, 112,140, 68, 183 and for Group 2: day 7, 14, 28, 56, 84, 112,140, 168,182, 210, 238, 252, 280, 308, 336, 350, 364.
measure: Average Daily Risperidone Implant Output During the Implant Phase
timeFrame: 6-months and 12-months for groups 1 and 2 respectively. Remaining Risperidone measurements taken at the end of the Implant Phase.
measure: Implant Device Placement Depth
timeFrame: Group 1 (6-month): Ultrasound on days 14 and 183. Group 2 (12-month): Ultrasound on days 14 and 364.
measure: Number of Participants Who Experienced Implant Migration in at Least One of the Implanted Devices
timeFrame: Group 1 (6-month): Assessments performed day 1 and day 183. Group 2 (12-month): Assessments performed day 1 and 364.
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Collaborative Neuroscience Research
state: California
city: Miami Lakes
country: United States
facility: Segal Trials
state: Florida
Study officials:
References: