Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Co-Administration of Roluperidone and Olanzapine in Adult Subjects With Moderate to Severe Negative Symptoms of Schizophrenia (NCT NCT06107803)
NCT ID: NCT06107803
Last Updated: 2025-03-26
Results Overview
AIMS is a rating scale to measure tardive dyskinesia (TD). For the scoring, the AIMS scale has 14 items. The first 10 items (under categories of Facial and Oral Movements, Extremity Movements, Trunk Movements, and Global Judgements) are rated from 0 (none) to 4 (severe); the remaining 4 items (Dental Status) are rated "yes" and "no" and not counted. The analysis is limited to items 1 to 10, with each rated from 0 to 4. The total score is the sum of all 10 items and with values ranging from 0 to 40. Overall change from baseline to End of Study (Day 17) in AIMS was reported for the Safety Set. Higher scores imply worse outcome.
COMPLETED
PHASE1
17 participants
Overall - Change from Baseline to End of Study (Day 17)
2025-03-26
Participant Flow
Participants underwent three study phases: Screening, Treatment Phase 1 and Treatment Phase 2.
Participant milestones
| Measure |
Overall Safety Set
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
|---|---|
|
Overall Study
STARTED
|
17
|
|
Overall Study
Full Set
|
17
|
|
Overall Study
Safety Set
|
17
|
|
Overall Study
Pharmacokinetic Set
|
12
|
|
Overall Study
Pharmacokinetic Completer Set
|
11
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Overall Safety Set
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
|---|---|
|
Overall Study
Adverse Event
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Protocol Violation
|
1
|
Baseline Characteristics
A Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Co-Administration of Roluperidone and Olanzapine in Adult Subjects With Moderate to Severe Negative Symptoms of Schizophrenia
Baseline characteristics by cohort
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
|---|---|
|
Age, Continuous
|
36.3 Years
STANDARD_DEVIATION 8.20 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
|
Body Mass Index at Baseline
|
27.3 kg/m2
STANDARD_DEVIATION 4.58 • n=5 Participants
|
PRIMARY outcome
Timeframe: Overall - Change from Baseline to End of Study (Day 17)AIMS is a rating scale to measure tardive dyskinesia (TD). For the scoring, the AIMS scale has 14 items. The first 10 items (under categories of Facial and Oral Movements, Extremity Movements, Trunk Movements, and Global Judgements) are rated from 0 (none) to 4 (severe); the remaining 4 items (Dental Status) are rated "yes" and "no" and not counted. The analysis is limited to items 1 to 10, with each rated from 0 to 4. The total score is the sum of all 10 items and with values ranging from 0 to 40. Overall change from baseline to End of Study (Day 17) in AIMS was reported for the Safety Set. Higher scores imply worse outcome.
Outcome measures
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Extrapyramidal Symptoms Assessed by Abnormal Involuntary Movement Scale (AIMS) - Change From Baseline in AIMS Component Movement
|
0.0 score on a scale
Standard Deviation 0.00
|
—
|
PRIMARY outcome
Timeframe: Overall - Change from Baseline to End of Study (Day 17)BARS is a multiple-choice questionnaire that clinicians may use to provide an assessment of akathisia. The clinician or rater is instructed to observe the subject while standing and while sitting, at least 2 minutes each (total of at least 4 minutes in total). There are 4 areas where the subject is to be evaluated, 1 of these is objective, 2 are subjective, and the final is a global assessment. The BARS scale has 3 items that are rated from 0 (absence/no distress) to 3 (most severe). The BARS rating scale is scored by summing the scales for Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness yielding a total score ranging from 0 to 9. The Total score, which has a possible range from 0-9, is reported. Higher scores imply worse outcome.
Outcome measures
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Barnes Akathisia Rating Scale (BARS)
|
0.0 score on a scale
Standard Deviation 0.00
|
—
|
PRIMARY outcome
Timeframe: Overall - End of Study (Day 17)C-SSRS is a measure to identify and assess individuals at risk for suicide. Questions are phrased for an interview format but can be completed as a self-report measure if needed. It measures 4 constructs: severity of ideation, intensity of ideation, behavior, and lethality. It includes "stem questions," which if endorsed, prompt additional follow-up questions to obtain more information. For the composite endpoint of suicidal ideation or behavior (1-10), the number and percent of subjects in the Overall Safety Set who experience any one of the ten suicidal ideation or behavior events at End of Study (Day 17).
Outcome measures
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Number of Subjects Who Experienced Suicidal Ideation or Behavior Events Per the Columbia Suicide Severity Rating Scale (C-SSRS)
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Days 1 through 17Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
Cmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Outcome measures
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
n=17 Participants
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax)
Treatment Phase 1 - Day 1
|
32.5 ng/ml
Standard Deviation 13.7
|
5.00 ng/ml
Standard Deviation 5.69
|
|
Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax)
Treatment Phase 1 - Day 7
|
43.6 ng/ml
Standard Deviation 19.9
|
7.98 ng/ml
Standard Deviation 6.78
|
|
Pharmacokinetic Evaluation of Roluperidone - Maximum Plasma Concentration (Cmax)
Treatment Phase 2 - Day 17
|
67.7 ng/ml
Standard Deviation 28.6
|
12.2 ng/ml
Standard Deviation 12.9
|
SECONDARY outcome
Timeframe: Days 1 through 17Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
Tmax of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Outcome measures
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
n=17 Participants
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax)
Treatment Phase 1 - Day 1
|
9.74 hr
Standard Deviation 7.37
|
16.2 hr
Standard Deviation 6.72
|
|
Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax)
Treatment Phase 1 - Day 7
|
7.47 hr
Standard Deviation 5.73
|
9.60 hr
Standard Deviation 6.02
|
|
Pharmacokinetic Evaluation of Roluperidone - Time to Maximum Plasma Concentration (Tmax)
Treatment Phase 2 - Day 17
|
6.20 hr
Standard Deviation 4.56
|
8.76 hr
Standard Deviation 4.90
|
SECONDARY outcome
Timeframe: Days 1 through 17Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Outcome measures
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
n=17 Participants
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24)
Treatment Phase 1 - Day 1
|
391 hr*ng/mL
Standard Deviation 252
|
52.3 hr*ng/mL
Standard Deviation 63.0
|
|
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24)
Treatment Phase 1 - Day 7
|
507 hr*ng/mL
Standard Deviation 278
|
135 hr*ng/mL
Standard Deviation 122
|
|
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC 0-24)
Treatment Phase 2 - Day 17
|
720 hr*ng/mL
Standard Deviation 321
|
203 hr*ng/mL
Standard Deviation 225
|
SECONDARY outcome
Timeframe: Days 1 through 17Population: Treatment Phase 1 - Day 7 had 15 participants analyzed. Treatment Phase 2 - Day 17 had 13 participants analyzed.
AUC of roluperidone and its metabolite following single dose and at steady state, and when administered concomitantly with olanzapine.
Outcome measures
| Measure |
Overall Safety Set
n=17 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
n=17 Participants
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf)
Treatment Phase 1 - Day 1
|
338 hr*ng/mL
Standard Deviation 289
|
60.7 hr*ng/mL
Standard Deviation 82.0
|
|
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf)
Treatment Phase 1 - Day 7
|
495 hr*ng/mL
Standard Deviation 272
|
168 hr*ng/mL
Standard Deviation 234
|
|
Pharmacokinetic Evaluation of Roluperidone - Area Under the Plasma Concentration Versus Time Curve (AUC Inf)
Treatment Phase 2 - Day 17
|
883 hr*ng/mL
Standard Deviation 420
|
263 hr*ng/mL
Standard Deviation 280
|
SECONDARY outcome
Timeframe: Treatment Phase 2 (Day 8 through Day 17)Cmax of olanzapine administered concomitantly with roluperidone
Outcome measures
| Measure |
Overall Safety Set
n=13 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Plasma PK Parameter for Olanzapine Cmax
|
35.6 ng/ml
Standard Deviation 12.7
|
—
|
SECONDARY outcome
Timeframe: Treatment Phase 2 (Day 8 through Day 17)Tmax of olanzapine administered concomitantly with roluperidone
Outcome measures
| Measure |
Overall Safety Set
n=13 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Plasma PK Parameter for Olanzapine Tmax
|
4.11 hr
Standard Deviation 2.24
|
—
|
SECONDARY outcome
Timeframe: Treatment Phase 2 (Day 8 through Day 17)AUC 0-24 olanzapine administered concomitantly with roluperidone
Outcome measures
| Measure |
Overall Safety Set
n=13 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Plasma PK Parameter for Olanzapine AUC 0-24
|
587 hr*ng/ml
Standard Deviation 220
|
—
|
SECONDARY outcome
Timeframe: Treatment Phase 2 (Day 8 through Day 17)AUC inf olanzapine administered concomitantly with roluperidone
Outcome measures
| Measure |
Overall Safety Set
n=13 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Plasma PK Parameter for Olanzapine AUC Inf
|
719 hr*ng/ml
Standard Deviation 144
|
—
|
SECONDARY outcome
Timeframe: Days 1 through 17Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for Cmax. The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite.
Outcome measures
| Measure |
Overall Safety Set
n=15 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
n=13 Participants
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax)
Roluperidone Analyte
|
39.8 ng/ml
Geometric Coefficient of Variation 46.37
|
62.2 ng/ml
Geometric Coefficient of Variation 44.78
|
|
Pharmacokinetic Evaluation of Co-administration Versus Roluperidone Monotherapy - Maximum Plasma Concentration (Cmax)
BFB-520 Analyte
|
5.96 ng/ml
Geometric Coefficient of Variation 89.12
|
8.54 ng/ml
Geometric Coefficient of Variation 100.10
|
SECONDARY outcome
Timeframe: Days 1 through 17Comparison of roluperidone on Day 17 with olanzapine to roluperidone alone on Day 7 for AUC 0-24. The geometric mean and geometric coefficient of variation are reported for the analytes roluperidone and its metabolite.
Outcome measures
| Measure |
Overall Safety Set
n=15 Participants
17 subjects were enrolled and received ≥ 1 dose of study drug and were included in the Safety Set.
|
Overall Safety Set - Metabolite BFB-520
n=13 Participants
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7 and concomitantly with olanzapine 10 mg daily on Days 8-17.
|
|---|---|---|
|
Pharmacokinetic Evaluation of Co-administration - AUC 0-24
Roluperidone Analyte
|
451 hr*ng/ml
Geometric Coefficient of Variation 50.50
|
656 hr*ng/ml
Geometric Coefficient of Variation 48.37
|
|
Pharmacokinetic Evaluation of Co-administration - AUC 0-24
BFB-520 Analyte
|
95.7 hr*ng/ml
Geometric Coefficient of Variation 103.10
|
135 hr*ng/ml
Geometric Coefficient of Variation 107.95
|
Adverse Events
Treatment Phase 1
Treatment Phase 2
Serious adverse events
| Measure |
Treatment Phase 1
n=17 participants at risk
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7.
Roluperidone 64 mg: 64 mg/day oral
|
Treatment Phase 2
n=15 participants at risk
Roluperidone 64 mg oral and olanzapine 10 mg oral administered at the same time daily for 10 days on Days 8-17.
Roluperidone 64 mg: 64 mg/day oral
Olanzapine 10 MG: 10 mg/day oral
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
5.9%
1/17 • Treatment through end of study (Day 17).
|
0.00%
0/15 • Treatment through end of study (Day 17).
|
Other adverse events
| Measure |
Treatment Phase 1
n=17 participants at risk
Roluperidone 64 mg monotherapy administered as an oral dose daily for 7 days on Days 1-7.
Roluperidone 64 mg: 64 mg/day oral
|
Treatment Phase 2
n=15 participants at risk
Roluperidone 64 mg oral and olanzapine 10 mg oral administered at the same time daily for 10 days on Days 8-17.
Roluperidone 64 mg: 64 mg/day oral
Olanzapine 10 MG: 10 mg/day oral
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
0.00%
0/17 • Treatment through end of study (Day 17).
|
20.0%
3/15 • Number of events 3 • Treatment through end of study (Day 17).
|
|
Nervous system disorders
Headache
|
11.8%
2/17 • Number of events 2 • Treatment through end of study (Day 17).
|
0.00%
0/15 • Treatment through end of study (Day 17).
|
|
Nervous system disorders
Somnolence
|
0.00%
0/17 • Treatment through end of study (Day 17).
|
13.3%
2/15 • Number of events 2 • Treatment through end of study (Day 17).
|
|
Nervous system disorders
Presyncope
|
5.9%
1/17 • Number of events 1 • Treatment through end of study (Day 17).
|
0.00%
0/15 • Treatment through end of study (Day 17).
|
|
Nervous system disorders
Syncope
|
0.00%
0/17 • Treatment through end of study (Day 17).
|
6.7%
1/15 • Number of events 1 • Treatment through end of study (Day 17).
|
|
Investigations
Alanine aminotransferase increased
|
5.9%
1/17 • Number of events 1 • Treatment through end of study (Day 17).
|
0.00%
0/15 • Treatment through end of study (Day 17).
|
|
Investigations
Blood creatine phosphokinase increased
|
5.9%
1/17 • Number of events 1 • Treatment through end of study (Day 17).
|
0.00%
0/15 • Treatment through end of study (Day 17).
|
|
Investigations
Electrocardiogram T wave inversion
|
0.00%
0/17 • Treatment through end of study (Day 17).
|
6.7%
1/15 • Number of events 1 • Treatment through end of study (Day 17).
|
|
Investigations
Heart rate increased
|
5.9%
1/17 • Number of events 1 • Treatment through end of study (Day 17).
|
0.00%
0/15 • Treatment through end of study (Day 17).
|
|
Psychiatric disorders
Agitation
|
5.9%
1/17 • Number of events 1 • Treatment through end of study (Day 17).
|
0.00%
0/15 • Treatment through end of study (Day 17).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place