Trial Outcomes & Findings for Study of BHV-4157 in Alzheimer's Disease (NCT NCT03605667)

Last Updated: 2023-12-06

Results Overview

The ADAS-Cog is a structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing a letter in an envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions were also obtained. The test was scored in terms of errors on a scale ranging from 0 (best) to 70 (worse), with higher scores indicate poorer performance and greater impairment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

350 participants

Primary outcome timeframe

Baseline (Day 1) and Week 48

Results posted on

2023-12-06

Participant Flow

This Phase 2, randomized, double-blind, placebo-controlled study was conducted in participants with mild to moderate alzheimer's disease (AD) at 44 centers in the US between 31-Jul-2018 and 23-Dec-2021.

A total of 687 participants were screened, of which 350 participants were randomized in a 1:1 ratio to receive troriluzole or placebo. 337 participants were not randomized due to screen failure, adverse events, lost to follow-up, withdrawal of consent, or unspecified reasons.

Participant milestones

Participant milestones
Measure	Troriluzole Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 milligrams (mg) capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase. Open-label extension (OLE) phase (48 weeks): Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks. OLE phase (48 weeks): Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Randomization Phase (Weeks 1 Through 48) STARTED	178	172
Randomization Phase (Weeks 1 Through 48) COMPLETED	130	133
Randomization Phase (Weeks 1 Through 48) NOT COMPLETED	48	39
OLE Phase (48 Weeks) STARTED	90	104
OLE Phase (48 Weeks) COMPLETED	35	24
OLE Phase (48 Weeks) NOT COMPLETED	55	80

Reasons for withdrawal

Reasons for withdrawal
Measure	Troriluzole Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 milligrams (mg) capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase. Open-label extension (OLE) phase (48 weeks): Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks. OLE phase (48 weeks): Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Randomization Phase (Weeks 1 Through 48) Withdrawal by Subject	18	19
Randomization Phase (Weeks 1 Through 48) Adverse Event	14	3
Randomization Phase (Weeks 1 Through 48) Other	1	4
Randomization Phase (Weeks 1 Through 48) Progressive disease	3	2
Randomization Phase (Weeks 1 Through 48) Lack of Efficacy	2	2
Randomization Phase (Weeks 1 Through 48) Physician Decision	2	3
Randomization Phase (Weeks 1 Through 48) Non-compliance with study drug	4	0
Randomization Phase (Weeks 1 Through 48) Protocol Violation	1	1
Randomization Phase (Weeks 1 Through 48) Lost to Follow-up	2	3
Randomization Phase (Weeks 1 Through 48) Death	1	2
OLE Phase (48 Weeks) Withdrawal by Subject	30	51
OLE Phase (48 Weeks) Other	6	8
OLE Phase (48 Weeks) Lack of Efficacy	6	5
OLE Phase (48 Weeks) Adverse Event	5	5
OLE Phase (48 Weeks) Progressive Disease	2	0
OLE Phase (48 Weeks) Physician Decision	5	7
OLE Phase (48 Weeks) Protocol Violation	0	1
OLE Phase (48 Weeks) Study Terminated By Sponsor	0	1
OLE Phase (48 Weeks) Death	0	2
OLE Phase (48 Weeks) Lost to Follow-up	1	0

Baseline Characteristics

Study of BHV-4157 in Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Troriluzole n=178 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase. OLE phase (48 weeks): Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo n=171 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks. OLE phase (48 weeks): Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Total n=349 Participants Total of all reporting groups
Age, Continuous	71.8 years STANDARD_DEVIATION 7.93 • n=5 Participants	71.6 years STANDARD_DEVIATION 7.91 • n=7 Participants	71.7 years STANDARD_DEVIATION 7.91 • n=5 Participants
Sex: Female, Male Female	110 Participants n=5 Participants	92 Participants n=7 Participants	202 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	79 Participants n=7 Participants	147 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	172 Participants n=5 Participants	165 Participants n=7 Participants	337 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	170 Participants n=5 Participants	163 Participants n=7 Participants	333 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 48

Population: Modified Intent to Treat (mITT) population included randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo) and who also had a baseline assessment and who have at least 1 efficacy evaluation following baseline. Participants results at Week 48 are reported.

Outcome measures

Outcome measures
Measure	Troriluzole n=119 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=127 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at Week 48	6.7 units on a scale Interval 5.3 to 8.1	6.7 units on a scale Interval 5.4 to 8.1	—	—

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 48

Population: The mITT population included randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo) and who also had a baseline assessment and who have at least 1 efficacy evaluation following baseline. Participants results at Week 48 are reported.

The CDR-sum of boxes is a validated composite rating of cognition and everyday functioning used in longitudinal AD research which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview 3 cognitive domains including memory, orientation, and judgement/problem solving and 3 everyday functional domains including community affairs, home and hobbies and personal care. The individual domain score ranging from 0 (none) to 3 (severe) but the scores in each of these were combined to obtain a composite score (sum of boxes) ranging from 0 (best) to 18 (worst), with higher scores indicate poorer performance and greater impairment. The individual domain scores are added to create a sum of the box scores.

Outcome measures

Outcome measures
Measure	Troriluzole n=118 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=127 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-Sum of Boxes) Total Score at Week 48	2.1 units on a scale Interval 1.7 to 2.5	1.9 units on a scale Interval 1.5 to 2.3	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

Volumetric MRI allows the in vivo assessment of brain structure volume and provides a measure of atrophy rate. Results from MRI studies suggest that the patterns of atrophy in AD, which mirror the pathological progression of the disease, can reliably be detected and tracked across time. Hippocampal volume derived from MRI correlates with histological hippocampal volume and degree of neuronal loss and AD pathology, and entorhinal cortical thickness change appears to be an early and sensitive indicator of neurodegeneration associated with AD.

Outcome measures

Outcome measures
Measure	Troriluzole n=87 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=90 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48	-1.1 percent deformation Interval -1.4 to -0.7	-1.1 percent deformation Interval -1.5 to -0.8	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

The ADCS-ADL inventory scale is validated questionnaire developed by the ADCS to assess instrumental and basic activities of daily living based on a 23-item structured interview of the AD study participant's partner. The scale ranging from 0 (none) to 78 (severe), with lower scores indicate greater impairment.

Outcome measures

Outcome measures
Measure	Troriluzole n=119 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=125 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 48	-8.9 units on a scale Interval -10.8 to -7.1	-7.4 units on a scale Interval -9.2 to -5.6	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology in AD dementia based on the results of an interview with the study partner. The NPI evaluates both the frequency and severity of 10 neuropsychiatric features, including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability and lability, and aberrant motor behavior, as well as evaluates sleep and appetite/eating disorders. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously). Severity assessments range from 1 (mild) to 3 (severe). The total score is the sum of all subscales ranging from 1 (mild) to 7 (severe), with higher scores indicate greater impairment.

Outcome measures

Outcome measures
Measure	Troriluzole n=120 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=125 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 48	2.3 units on a scale Interval 0.2 to 4.4	3.8 units on a scale Interval 1.8 to 5.8	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 48

The MMSE is a frequently used screening instrument for AD drug studies. It evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy 2 intersecting pentagons. The MMSE scale ranging from 0 (worse) to 30 (best), with a lower score indicate more cognitive impairment.

Outcome measures

Outcome measures
Measure	Troriluzole n=121 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=128 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Change From Baseline in Mini-Mental Status Examination (MMSE) Total Score at Week 48	-3.6 units on a scale Interval -4.4 to -2.9	-3.2 units on a scale Interval -4.0 to -2.5	—	—

SECONDARY outcome

Timeframe: TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks.

Population: Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).

An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is defined as any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received study drug; other important medical events that may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the other serious outcomes. An AE is considered "Related" for causality designations of possible, probable and definite.

Outcome measures

Outcome measures
Measure	Troriluzole n=178 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=171 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase n=90 Participants Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase n=103 Participants Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Any TEAEs	146 Participants	116 Participants	57 Participants	66 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Any serious TEAEs	24 Participants	14 Participants	9 Participants	16 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Any fatal AE	2 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Any serious TEAEs considered related	3 Participants	1 Participants	0 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Drug withdrawn due to an TEAE	16 Participants	3 Participants	5 Participants	12 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Day 1) and Week 48

Subgroup of participants MMSE Category = Mild. The MMSE scale ranging from 0 (worse) to 30 (best), with a lower score indicating more cognitive impairment. Mild are participants with a baseline MMSE score greater than or equal to 20.

Outcome measures

Outcome measures
Measure	Troriluzole n=48 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=49 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48 in Mild Subgroup	-1.1 percent deformation Interval -1.6 to -0.6	-1.6 percent deformation Interval -2.1 to -1.0	—	—

POST_HOC outcome

Timeframe: Baseline (Day 1) and Week 48

Mild APOE e4 carrier subgroup are participants with a baseline MMSE score greater than or equal to 20 with APOE e4 genotype. Responder based on ADAS-cog Total Change less than or equal to 1 and MRI Hippocampal Volume Change greater than or equal to -2.09. ADAS-cog change and MRI Hippcampal volume change criteria based on 25th percentile.

Outcome measures

Outcome measures
Measure	Troriluzole n=45 Participants Randomization phase (Randomization through Week 48): Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo n=44 Participants Randomization phase (Randomization through Week 48): Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Number of Responders in Participants With ADAS-cog Total Change and MRI Hippocampal Volume Change at Week 48 in Mild APOE e4 Carrier Subgroup	14 Participants	4 Participants	—	—

Adverse Events

Troriluzole - Randomization Phase

Serious events: 24 serious events

Other events: 81 other events

Deaths: 2 deaths

Placebo - Randomization Phase

Serious events: 14 serious events

Other events: 53 other events

Deaths: 2 deaths

Troriluzole - Randomization Phase/ Troriluzole - OLE Phase

Serious events: 9 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo - Randomization Phase/ Troriluzole - OLE Phase

Serious events: 16 serious events

Other events: 31 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Troriluzole - Randomization Phase n=178 participants at risk Participants received starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg once daily for the remaining 46 weeks of the double-blind phase.	Placebo - Randomization Phase n=171 participants at risk Participants received placebo matching with troriluzole for 48 weeks.	Troriluzole - Randomization Phase/ Troriluzole - OLE Phase n=90 participants at risk Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.	Placebo - Randomization Phase/ Troriluzole - OLE Phase n=103 participants at risk Participants who completed the double-blind treatment phase were offered the opportunity to enroll in an OLE phase to receive starting dose of troriluzole 140 mg capsules orally once daily for 2 weeks, followed by 280 mg orally once daily for the remaining 46 weeks.
Gastrointestinal disorders Diarrhoea	8.4% 15/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	3.5% 6/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	1.1% 1/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	2.9% 3/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
General disorders Oedema peripheral	5.1% 9/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	1.2% 2/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	0.00% 0/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	0.00% 0/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Infections and infestations Coronavirus infection	0.00% 0/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	0.00% 0/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	5.6% 5/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	0.97% 1/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Infections and infestations Urinary tract infection	8.4% 15/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	7.0% 12/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	5.6% 5/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	4.9% 5/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Injury, poisoning and procedural complications Fall	10.7% 19/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	6.4% 11/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	11.1% 10/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	6.8% 7/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Investigations Liver function test increased	2.8% 5/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	0.00% 0/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	2.2% 2/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	5.8% 6/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Investigations Weight decreased	9.0% 16/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	2.3% 4/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	0.00% 0/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	1.9% 2/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Metabolism and nutrition disorders Decreased appetite	9.0% 16/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	1.2% 2/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	1.1% 1/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	0.97% 1/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Nervous system disorders Dizziness	5.6% 10/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	7.6% 13/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	3.3% 3/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	1.9% 2/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Nervous system disorders Headache	3.4% 6/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	8.2% 14/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	3.3% 3/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	2.9% 3/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).
Psychiatric disorders Anxiety	5.1% 9/178 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	4.1% 7/171 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	3.3% 3/90 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).	2.9% 3/103 • TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks. Treated population included enrolled and randomized participants who received at least 1 dose of blinded study therapy (troriluzole or placebo).

Additional Information

Chief Medical Officer

Biohaven Pharmaceuticals, Inc

Phone: +1 203-404-0410

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60