Safety and Tolerability of Risperidone Implants

• Sponsor: Braeburn Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02773576
• Collaborator: (none)
• Enrollment: 140
• Location: 1
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site Per Month: 8.2

Study Details

Study Description

Brief Summary

A one year, open-label, study to evaluate the safety and tolerability of risperidone implants as a maintenance treatment in patients with schizophrenia

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia	Drug: Risperidone implant	Phase 3

Detailed Description

The trial is to evaluate the 48-week safety and tolerability of risperidone implants as maintenance therapy in subjects with schizophrenia. This will be measured by the incidence of psychotic symptoms exacerbation/impending relapse, PANSS, CGI-I, CGI-S, adverse events, vital signs, clinical laboratory, physical exam and ECG findings, Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Scale (SAS) and Investigator assessments.

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A One Year, Open-label, Study to Evaluate the Safety and Tolerability of Risperidone Implants as a Maintenance Treatment in Patients With Schizophrenia
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2x360 mg risperidone implant 2, 360 mg risperidone implants	Drug: Risperidone implant
Experimental: 3x300 mg risperidone implant 3, 300 mg risperidone implants	Drug: Risperidone implant

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-related Adverse Events as Assessed [12 months]

   The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.

Secondary Outcome Measures

1. Incidence of Psychotic Symptom Exacerbation/Impending Relapse [12 months]

   The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.

Other Outcome Measures

1. Change of Sleep Quality From Baseline to Month 12 Measured on the Pittsburgh Sleep Quality Index (PSQI) [Baseline and 12 months]

   The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has provided written informed consent.

2. Male and female subjects 18 to 70 years of age, inclusive, at time of informed consent.

3. Subjects with a current diagnosis of schizophrenia as defined by DSM-5 criteria and a history of the illness for at least 2 years prior to screening (as per subject, family, healthcare provider, and/or by previous medical records).

4. Subject is assessed by the Investigator to be symptomatically stable with regard to his or her psychiatric condition at screening and baseline.

5. Subject must be stable on their current antipsychotic medication for at least 30 days prior to screening.

6. Subject has identified a caregiver or personal contact with whom the subject has significant contact with at least once per week.

7. Subjects who have shown a previous response to antipsychotic treatment (other than clozapine) in the past year, according to the Investigator's opinion.

8. Subjects who are currently being treated with one or two antipsychotics other than clozapine, and who, in the Investigator's judgment, require chronic treatment with an antipsychotic medication and would benefit from treatment with Risperidone Implants.

9. Subjects who meet the following criteria:

10. Outpatient status

11. PANSS Total Score ≤ 80, and if PANSS score at baseline increases by ≥ 20% change from screening, the subject cannot participate in the study.

12. PANSS scores of ≤ 4 on all of the following items:

• Conceptual disorganization

• Suspiciousness

• Hallucinatory behavior

• Unusual thought content

• Hostility

1. CGI-S ≤ 4 (moderately ill)

2. Lack of clinically significant suicidal ideation or behavior in Investigator's judgment

3. Subjects who are able to understand the nature of the trial and follow protocol requirements, have the ability to read and understand the written word, and who can be reliably rated on assessment scales.

4. Subjects who have completed adequate washout (5 half-lives unless otherwise specified) of prohibited concomitant medications, including mood stabilizers and strong inducers or inhibitors of CYP2D6 activity, prior to receiving oral risperidone or implant Risperidone.

5. Subject has completed washout of 42 days for any fluoxetine containing compound.

6. Female participants (if of childbearing potential and sexually active) and male participants (if sexually active with a partner of childbearing potential) who agree to use a medically acceptable and effective birth control method throughout the study.

7. Subject has a body mass index (BMI) ≥18.5 and ≤38.0 kg/m2.

8. Subject 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. Known hypersensitivity or allergy to lidocaine or any local anesthetic agent of the amide type (local anesthetic used during implant and explant procedures).

2. Known sensitivity to polyurethane.

3. Reports or reveals a presence of clinically significant skin disorders (such as, but not limited to, skin cancer, psoriasis, eczema, or atopic dermatitis), and/or 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.

4. History of abnormal scar formation or family history of keloid formation.

5. Subjects with a current DSM-5 diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder are excluded.

6. Subjects experiencing acute depressive symptoms within the past 30 days, according to the Investigator's opinion, that required treatment with an antidepressant.

7. Subjects considered by the Investigator to be at imminent risk of suicide or injury to self, or subjects who within the past 6 months prior to Screening have attempted suicide, or who within the past 3 months prior to Screening have had active suicide ideation (positive answers to item 4 or 5 on the C-SSRS).

8. Subjects with schizophrenia that are considered resistant/refractory to antipsychotic treatment by history.

9. Subjects with a history of failure to clozapine treatment or response to clozapine treatment only.

10. Subjects with a documented history of failure to respond to an adequate dose of risperidone or paliperidone treatment including long acting injectable formulations.

11. Subjects with a significant risk of violent behavior or a significant risk of committing suicide based on history or Investigator's judgment.

12. Subjects who currently meet DSM-5 criteria for substance use disorder (moderate or severe); including alcohol and benzodiazepines, but excluding caffeine, nicotine, and marijuana.

13. Females who are breast-feeding or will be breast feeding during the course of the study, and/or who have a positive serum pregnancy test result prior to receiving trial medication.

14. Subjects with uncontrolled hypothyroidism or hyperthyroidism (unless condition has been stabilized with medications for at least the past 90 days).

15. Subjects who have a clinically significant history or evidence of a medical condition that would expose them to an undue risk of a significant AE or interfere with assessments of safety or efficacy during the course of the trial.

16. Subjects with epilepsy or a history of seizures, except for a single childhood febrile seizure, post traumatic, alcohol withdrawal, etc. A subject with a history of any seizure activity will have their case discussed with the medical monitor prior to subject's study enrollment.

17. Subjects with a positive drug screen at screening for drugs of abuse without a prescription, excluding marijuana, will be discussed with the medical monitor.

18. The following laboratory test, vital sign, and ECG results are exclusionary:

19. Platelets ≤ 75,000/mm3

20. Hemoglobin ≤ 9 g/dL

21. Neutrophils, absolute ≤ 1000/mm3

22. Aspartate aminotransferase > 3x upper limit of normal

23. Alanine aminotransferase > 3x upper limit of normal

24. Creatinine ≥ 2 mg/dL

25. Diastolic blood pressure > 105 mmHg

26. QTc > 470 msec for females and QTc > 450 msec for males using the QTcF (Fridericia) correction

27. Subject is HIV positive.

28. Active hepatitis. Subjects with no viral load, no acute inflammation and no clinical necessity for therapy will be allowed, at the discretion of the Investigator.

29. Subjects with a history of an allergic hypersensitivity to antipsychotic agents.

30. Subjects with a history of significant intolerance or who are refractory to antipsychotic agents.

31. Subjects with a history of neuroleptic malignant syndrome.

32. Subjects with clinically significant tardive dyskinesia at screening [any one AIMS item (1-7) with a score >2].

33. Subjects likely to require prohibited concomitant therapy during the trial (see Section 8.6.1).

34. Subjects who require current use of agents that are strong inhibitors (e.g. quinidine) and inducers (e.g. carbamazepine, phenytoin, rifampin, and phenobarbital) of cytochrome P450 2D6.

35. Subjects who have received any investigational agent in a clinical trial within 30 days prior to screening; for investigational drugs with an elimination half-life greater than 15 days, this time period will be extended to 60 days.

36. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness, or who have ongoing legal issues that could affect their ability to continue to participate in this trial.

37. Subjects who have been hospitalized, including hospitalization for psychosocial reasons, for more than 30 days total in the last 60 days prior to entry into the Screening Phase.

38. Electroconvulsive therapy within 180 days prior to entry into the Screening Phase.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Collaborative Neuroscience Network	Garden Grove	California	United States	92845

Sponsors and Collaborators

• Braeburn Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 15, 2016

More Information

Publications

None provided.

• Responsible Party: Braeburn Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02773576
• Other Study ID Numbers: BB-RSP-301
• First Posted: May 16, 2016
• Last Update Posted: Feb 19, 2020
• Last Verified: Feb 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Schizophrenia; Risperidone

Study Results

Participant Flow

Pre-assignment Detail	The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study

Arm/Group Title	2x360 mg Risperidone Implant	3x300 mg Risperidone Implant
Arm/Group Description	2, 360 mg risperidone implants Risperidone implant	3, 300 mg risperidone implants Risperidone implant
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	2x360 mg Risperidone Implant	3x300 mg Risperidone Implant	Total
Arm/Group Description	2, 360 mg risperidone implants Risperidone implant	3, 300 mg risperidone implants Risperidone implant	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male
Race (NIH/OMB) () []
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-related Adverse Events as Assessed
Description	The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.

Arm/Group Title	2x360 mg Risperidone Implant	3x300 mg Risperidone Implant
Arm/Group Description	2, 360 mg risperidone implants Risperidone implant	3, 300 mg risperidone implants Risperidone implant
Measure Participants	0	0

2. Secondary Outcome

Title	Incidence of Psychotic Symptom Exacerbation/Impending Relapse
Description	The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.

Arm/Group Title	2x360 mg Risperidone Implant	3x300 mg Risperidone Implant
Arm/Group Description	2, 360 mg risperidone implants Risperidone implant	3, 300 mg risperidone implants Risperidone implant
Measure Participants	0	0

3. Other Pre-specified Outcome

Title	Change of Sleep Quality From Baseline to Month 12 Measured on the Pittsburgh Sleep Quality Index (PSQI)
Description	The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.

Arm/Group Title	2x360 mg Risperidone Implant	3x300 mg Risperidone Implant
Arm/Group Description	2, 360 mg risperidone implants Risperidone implant	3, 300 mg risperidone implants Risperidone implant
Measure Participants	0	0

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.
Arm/Group Title	2x360 mg Risperidone Implant		3x300 mg Risperidone Implant
Arm/Group Description	2, 360 mg risperidone implants Risperidone implant		3, 300 mg risperidone implants Risperidone implant
All Cause Mortality
	2x360 mg Risperidone Implant		3x300 mg Risperidone Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	2x360 mg Risperidone Implant		3x300 mg Risperidone Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	2x360 mg Risperidone Implant		3x300 mg Risperidone Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

The product was sold to another company prior to data analysis. The new company closed before the results were completed, so no results are available for this study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.