Trial Outcomes & Findings for A Trial to Evaluate the Efficacy and Safety of PQ912 in Patients With Early AD (NCT NCT03919162)

NCT ID: NCT03919162

Last Updated: 2025-12-12

Results Overview

The proportion of participants, who experience any AESI during the safety evaluation period, which is from first dose to completion of 8 weeks at the full originally assigned dose. Per protocol, if the first cohort (Cohort A) does not meet the pre-specified Pocock safety stopping boundary within the active arm, that dose will be selected as safe. The dose selected as safe will be the dose carried forward for all participants in the active arm for the remainder of the study. The Pocock boundary is only valid until dose selection. If a higher dose is selected as safe, assignment to lower doses will stop, and all current participants on a lower dose will be titrated up to the selected dose according to uptitration schedule. If Cohort A does not meet the Pocock boundary only evaluation of Cohort A is required for this endpoint.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 112 participants
• Primary outcome timeframe: From first dose to completion of 8 weeks on the full dose (Week 16)
• Results posted on: 2025-12-12

Participant Flow

Participants were enrolled at 22 study centers in the US between 2021 and 2024. The first participant was screened on November 10, 2021 and the last participant had his last visit on August 12, 2024. Of 253 screened participants, 112 met inclusion criteria and were randomized to treatment.

Participants were randomized 1:1 to PQ912 or matching placebo. All participants randomized to PQ912 started at 150 mg BID and were up-titrated to 600 mg BID. Therefore, all data from the participants randomized to PQ912 were collected as one single active Arm/Group and separation of doses is not applicable. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.

Participant milestones

Measure	PQ912 All participants started at 150 mg BID and were up-titrated to 600 mg BID administered orally for up to 72 weeks and therefore, all data from these participants were collected as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B. PQ912: 150 mg tablets	Placebo All participants received matching placebo BID administered orally for up to 72 weeks Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B. Placebo: PQ912 matching placebo tablet
Overall Study STARTED	53	59
Overall Study Treated	52	57
Overall Study COMPLETED	13	20
Overall Study NOT COMPLETED	40	39

Reasons for withdrawal

Measure	PQ912 All participants started at 150 mg BID and were up-titrated to 600 mg BID administered orally for up to 72 weeks and therefore, all data from these participants were collected as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B. PQ912: 150 mg tablets	Placebo All participants received matching placebo BID administered orally for up to 72 weeks Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B. Placebo: PQ912 matching placebo tablet
Overall Study Adverse Event	3	2
Overall Study Death	2	0
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	12	12
Overall Study Study terminated by Sponsor	20	24
Overall Study Screen failure	1	0
Overall Study Missing	1	1

Baseline Characteristics

Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.

Baseline characteristics by cohort

Measure	PQ912 n=52 Participants All participants started at 150 mg BID and were up-titrated to 600 mg BID administered orally for up to 72 weeks and therefore, all data from these participants were collected as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B. PQ912: 150 mg tablets	Placebo n=57 Participants All participants received matching placebo BID administered orally for up to 72 weeks Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B. Placebo: PQ912 matching placebo tablet	Total n=109 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=52 Participants	0 Participants n=57 Participants	0 Participants n=109 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=52 Participants	11 Participants n=57 Participants	19 Participants n=109 Participants
Age, Categorical >=65 years	44 Participants n=52 Participants	46 Participants n=57 Participants	90 Participants n=109 Participants
Age, Continuous	72.9 Years STANDARD_DEVIATION 8.3 • n=52 Participants	70.8 Years STANDARD_DEVIATION 7.4 • n=57 Participants	71.8 Years STANDARD_DEVIATION 7.9 • n=109 Participants
Sex: Female, Male Female	24 Participants n=52 Participants	30 Participants n=57 Participants	54 Participants n=109 Participants
Sex: Female, Male Male	28 Participants n=52 Participants	27 Participants n=57 Participants	55 Participants n=109 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=52 Participants	0 Participants n=57 Participants	2 Participants n=109 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=52 Participants	57 Participants n=57 Participants	107 Participants n=109 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=52 Participants	0 Participants n=57 Participants	0 Participants n=109 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=52 Participants	0 Participants n=57 Participants	0 Participants n=109 Participants
Race (NIH/OMB) Asian	0 Participants n=52 Participants	1 Participants n=57 Participants	1 Participants n=109 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=52 Participants	0 Participants n=57 Participants	0 Participants n=109 Participants
Race (NIH/OMB) Black or African American	1 Participants n=52 Participants	4 Participants n=57 Participants	5 Participants n=109 Participants
Race (NIH/OMB) White	51 Participants n=52 Participants	52 Participants n=57 Participants	103 Participants n=109 Participants
Race (NIH/OMB) More than one race	0 Participants n=52 Participants	0 Participants n=57 Participants	0 Participants n=109 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=52 Participants	0 Participants n=57 Participants	0 Participants n=109 Participants
Region of Enrollment United States	52 participants n=52 Participants	57 participants n=57 Participants	109 participants n=109 Participants
Alzheimer's Disease Neuroimaging Initiative (ADNI) Battery Composite (ABC) score	-0.01 Z-scores STANDARD_DEVIATION 0.65 • n=52 Participants	0.00 Z-scores STANDARD_DEVIATION 0.58 • n=57 Participants	-0.00 Z-scores STANDARD_DEVIATION 0.61 • n=109 Participants
Apolipoprotein E (APOE) genotyping E4 carrier - homozygous	11 Participants n=52 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.	14 Participants n=55 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.	25 Participants n=107 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.
Apolipoprotein E (APOE) genotyping E4 carrier - heterozygous	23 Participants n=52 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.	30 Participants n=55 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.	53 Participants n=107 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.
Apolipoprotein E (APOE) genotyping Non-carrier	18 Participants n=52 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.	11 Participants n=55 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.	29 Participants n=107 Participants • Two patients not included in the denominator for the calculation of percentages because of missing APOE genotype data.
Clinical Dementia Rating - Sum of Boxes (CDR-SB)	3.35 Box scores (0-18) STANDARD_DEVIATION 1.53 • n=52 Participants	2.99 Box scores (0-18) STANDARD_DEVIATION 1.70 • n=57 Participants	3.16 Box scores (0-18) STANDARD_DEVIATION 1.62 • n=109 Participants
Quantitative EEG (qEEG)	0.18952 Proportion (0-1) STANDARD_DEVIATION 0.09281 • n=25 Participants • Only paired EEGs (at least 1 Baseline and 1 Follow-up EEG) were analyzed.	0.13596 Proportion (0-1) STANDARD_DEVIATION 0.05351 • n=27 Participants • Only paired EEGs (at least 1 Baseline and 1 Follow-up EEG) were analyzed.	0.16171 Proportion (0-1) STANDARD_DEVIATION 0.07902 • n=52 Participants • Only paired EEGs (at least 1 Baseline and 1 Follow-up EEG) were analyzed.
Initial diagnosis Mild cognitive impairment due to Alzheimer's disease	30 Participants n=52 Participants	38 Participants n=57 Participants	68 Participants n=109 Participants
Initial diagnosis Mild probable Alzheimer's disease	22 Participants n=52 Participants	19 Participants n=57 Participants	41 Participants n=109 Participants
Site Northern Light Acadia Hospital (AHEMMC)	5 Participants n=52 Participants	4 Participants n=57 Participants	9 Participants n=109 Participants
Site Banner Sun Health Research Institute (BSHRI)	4 Participants n=52 Participants	5 Participants n=57 Participants	9 Participants n=109 Participants
Site Northwestern University Feinberg School of Medicine (NWU)	3 Participants n=52 Participants	5 Participants n=57 Participants	8 Participants n=109 Participants
Site Ohio State University (OSU)	9 Participants n=52 Participants	8 Participants n=57 Participants	17 Participants n=109 Participants
Site Lowcountry Center for Veterans Research (RJVA)	3 Participants n=52 Participants	3 Participants n=57 Participants	6 Participants n=109 Participants
Site University of California, Irvine (UCI)	4 Participants n=52 Participants	3 Participants n=57 Participants	7 Participants n=109 Participants
Site University of California San Diego (UCSD) Alzheimer's Disease Research Center	4 Participants n=52 Participants	6 Participants n=57 Participants	10 Participants n=109 Participants
Site The University of Iowa Carver College of Medicine (UI)	5 Participants n=52 Participants	5 Participants n=57 Participants	10 Participants n=109 Participants
Site The University of Kentucky Sanders-Brown Center on Aging (UKY)	3 Participants n=52 Participants	3 Participants n=57 Participants	6 Participants n=109 Participants
Site Pooled sites	12 Participants n=52 Participants	15 Participants n=57 Participants	27 Participants n=109 Participants

PRIMARY outcome

Timeframe: From first dose to completion of 8 weeks on the full dose (Week 16)

Population: All participants started at 150 mg BID and were up-titrated to 600 mg BID. As pre-specified, this endpoint presents data from first 60 participants (Cohort A) after completion of 8 weeks on full dose, 600 mg BID, because Pocock safety stopping boundary applies only until dose selection.

The proportion of participants, who experience any AESI during the safety evaluation period, which is from first dose to completion of 8 weeks at the full originally assigned dose. Per protocol, if the first cohort (Cohort A) does not meet the pre-specified Pocock safety stopping boundary within the active arm, that dose will be selected as safe. The dose selected as safe will be the dose carried forward for all participants in the active arm for the remainder of the study. The Pocock boundary is only valid until dose selection. If a higher dose is selected as safe, assignment to lower doses will stop, and all current participants on a lower dose will be titrated up to the selected dose according to uptitration schedule. If Cohort A does not meet the Pocock boundary only evaluation of Cohort A is required for this endpoint.

Outcome measures

Measure	PQ912 n=27 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=33 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2A: Number of Participants With Any Adverse Event of Special Interest (AESI)	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Week 24, pre-dose (trough level) and 2-3h post-dose

Population: Pharmacokinetic population, including all randomized participants who have received at least 1 dose of the study drug, and who provided sufficient PK samples to reliably estimate 1 plasma PK concentration post-baseline

The pharmacokinetics (PK) endpoints in Phase 2A are the derived median values of PQ912 levels in plasma and the corresponding calculated target occupancy (TO) in CSF, following at least 8 weeks of treatment at the dose level being tested. TO in CSF was estimated from plasma PQ912 concentrations.

Outcome measures

Measure	PQ912 n=37 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo All participants received placebo BID administered orally for 16 weeks
Phase 2A: Median Estimated Target Occupancy (TO) of PQ912 in Cerebrospinal Fluid (CSF) at Week 24 Week 24 (Visit 7) - pre-dose	55.3 Percent (%) Interval 0.0 to 86.4	—
Phase 2A: Median Estimated Target Occupancy (TO) of PQ912 in Cerebrospinal Fluid (CSF) at Week 24 Week 24 (Visit 7) - 2-3h post-dose	94.3 Percent (%) Interval 31.6 to 97.7	—

PRIMARY outcome

Timeframe: Week 24, pre-dose (trough level) and 2-3h post-dose

Population: Pharmacokinetic population, including all randomized participants who have received at least 1 dose of the study drug, and who provided sufficient PK samples to reliably estimate 1 plasma PK concentration post-baseline

The pharmacokinetics (PK) endpoints in Phase 2A are the derived median values of PQ912 levels in plasma and the corresponding calculated target occupancy (TO) in CSF, following at least 8 weeks of treatment at the dose level being tested.

Blood samples were obtained and PQ912 plasma concentrations were determined using a validated high-pressure liquid chromatography hyphenated with tandem mass spectrometry (LC-MS/MS) method.

Outcome measures

Measure	PQ912 n=37 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo All participants received placebo BID administered orally for 16 weeks
Phase 2A: Median Plasma Concentrations of PQ912 at Week 24 Week 24 (Visit 7) - pre-dose	208.0 ng/mL Interval 0.0 to 1070.0	—
Phase 2A: Median Plasma Concentrations of PQ912 at Week 24 Week 24 (Visit 7) - 2-3h post-dose	2790.0 ng/mL Interval 77.7 to 7210.0	—

PRIMARY outcome

Timeframe: 24 weeks

Population: The mITT population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB)

The within-participant change from baseline in the composite mean of standardized scores from a set of ADNI neuropsychological test measures, the ADNI Battery Composite (ABC, 9-item).

The ABC score was calculated from the following 9 measures from the ADNI-1 Neuropsychological Test Battery: Auditory Verbal Learning Test (AVLT)-Immediate Recall, AVLT-Delayed Recall, Number Span Forward, Number Span Backward, Category Fluency, Trail Making Test A, Trail Making Test B, Digit Symbol Substitution, Boston Naming Test. Standardized scores (Z-scores) were calculated using the overall mean and standard deviation of all participants in the modified Intent-to-Treat (mITT) population at baseline as reference.

The ABC score for each participant was the mean of the standardized subtest values. Range: -3 to 3; higher scores indicate less impairment.

Outcome measures

Measure	PQ912 n=49 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=53 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2A: Change From Baseline in Alzheimer's Disease Neuroimaging Initiative (ADNI) Battery Composite (ABC) Score	-0.156 Z-scores Standard Error 0.036	-0.214 Z-scores Standard Error 0.039

PRIMARY outcome

Timeframe: 24 weeks

Population: The modified intent-to-treat (mITT) population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB). Only paired EEGs (at least 1 evaluable Baseline and 1 evaluable Follow-up EEG) were analyzed.

The within-participant change from baseline of global relative theta wave power (4-8 Hz) in qEEG. qEEG was used to assess resting-state brain activity, including global relative theta power (4-8 Hz), based on spectral analysis of signals from 21 electrode positions. Higher theta power indicates greater impairment.

Outcome measures

Measure	PQ912 n=24 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=25 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2A: Change From Baseline in Quantitative Electroencephalogram (qEEG)	0.01749 Proportion (0-1) Standard Error 0.00649	0.02275 Proportion (0-1) Standard Error 0.00619

PRIMARY outcome

Timeframe: 72 weeks

Population: The modified intent-to-treat (mITT) population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for Phase 2B (CDR-SB)

The within-participant change from baseline in CDR-SB scores. The CDR-SB is a composite rating of cognition and everyday function which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview three cognitive domains (memory, orientation, and judgement/problem solving) and three everyday functional domains (community affairs, home and hobbies, and personal care). Level of impairment in each of the six domains is rated from none (score=0) to severe (score=3). The six domain scores are then summed to create the CDR-SB. Range: 0-18; higher scores indicate greater impairment.

Outcome measures

Measure	PQ912 n=17 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=22 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score	1.63 Box scores (0-18) Standard Error 0.36	1.68 Box scores (0-18) Standard Error 0.34

SECONDARY outcome

Timeframe: 72 weeks

Population: The modified intent-to-treat (mITT) population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB)

The within-participant change from baseline in CFC2 scores. The CFC2 is a novel composite outcome measure of cognition and everyday function that has been derived from measures used in Alzheimer's Disease Neuroimaging Initiative (ADNI) and optimized for detecting change in early Alzheimer's disease (doi.org/10.1016/j.jalz.2012.05.2187). CFC2 is comprised of selected subtests from the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) (Word Recall, Delayed Word Recall, and Orientation), Clinical Dementia Rating (CDR) sum of the Cognitive Boxes (Memory, Orientation, Judgement, and Problem Solving), and the Functional Activities Questionnaire (FAQ). The total score for each component subtest was multiplied by -1 so that higher scores indicate better performance. The CFC2 score was then calculated as the sum of the transformed raw scores for the component subtests. Range: -67 to 0; higher scores indicate less impairment.

Outcome measures

Measure	PQ912 n=16 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=20 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Key Secondary Efficacy: Change From Baseline in Cognitive Functional Composite-2 (CFC2) Score, a Cognitive Functional Composite	-6.694 Total score (-67 to 0) Standard Error 1.613	-7.664 Total score (-67 to 0) Standard Error 1.512

SECONDARY outcome

Timeframe: 72 weeks

Population: The modified mITT population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB)

The within-participant change from baseline in the composite sum of standardized scores from a set of ADNI neuropsychological test measures, the ADNI Battery Composite (ABC, 9-item). The ABC score is calculated from the following 9 measures from the ADNI-1 Neuropsychological Test Battery: Auditory Verbal Learning Test (AVLT)-Immediate Recall, AVLT-Delayed Recall, Number Span Forward, Number Span Backward, Category Fluency, Trail Making Test A, Trail Making Test B, Digit Symbol Substitution, Boston Naming Test. Standardized scores (Z-scores) were calculated using the overall mean and standard deviation of all participants in the modified intent-to-treat (mITT) population at baseline as reference. The ABC score for each participant was the mean of the standardized subtest values. Range: -3 to 3; higher scores indicate less impairment.

Outcome measures

Measure	PQ912 n=15 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=21 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Change From Baseline in Alzheimer's Disease Neuroimaging Initiative (ADNI) Battery Composite (ABC, 9-item) Score	-0.278 Z-scores Standard Error 0.078	-0.378 Z-scores Standard Error 0.069

SECONDARY outcome

Timeframe: 72 weeks

Population: The modified intent-to-treat (mITT) population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB). Only paired EEGs (at least 1 evaluable Baseline and 1 evaluable Follow-up EEG) were analyzed.

The within-participant change from baseline of global relative theta wave power (4-8 Hz) in qEEG. qEEG was used to assess resting-state brain activity, including global relative theta power (4-8 Hz), based on spectral analysis of signals from 21 electrode positions. Higher theta power indicates greater impairment.

Outcome measures

Measure	PQ912 n=8 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=10 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Change From Baseline in Quantitative Electroencephalogram (qEEG)	-0.01123 Proportion (0-1) Standard Error 0.01474	0.01734 Proportion (0-1) Standard Error 0.01291

SECONDARY outcome

Timeframe: 72 weeks

Population: The modified intent-to-treat (mITT) population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB)

The within-participant change from baseline in FAQ.The FAQ is a validated 10-item questionnaire, completed as a structured interview with the study partner, which rates the study participant's ability to carry out ten complex activities of daily living (doi.org/10.1093/geronj/37.3.323). Each item is rated on a scale from 0 (no impairment) to 3 (dependent). Scores are summed across items to provide a total score. Range: 0 to 30; higher scores indicate greater impairment.

Outcome measures

Measure	PQ912 n=17 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=22 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Change From Baseline in Functional Activities Questionnaire (FAQ)	4.36 Total score (0-30) Standard Error 1.35	4.97 Total score (0-30) Standard Error 1.23

SECONDARY outcome

Timeframe: 72 weeks

Population: The modified intent-to-treat (mITT) population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB)

The within-participant change from baseline in ADAS-Cog-13. The ADAS-Cog-13 is a structured scale that evaluates memory (immediate and delayed word recall; immediate word recognition), receptive and expressive language, orientation, ideational praxis (preparing a letter for mailing), constructional praxis (copying figures), and attention (number cancellation). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions also are obtained. The ADAS-Cog total score is calculated by summing the scores of the 13 component subtests. Range: 0-85; higher scores indicate greater impairment.

Outcome measures

Measure	PQ912 n=14 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=19 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog-13)	6.377 Total score (0-85) Standard Error 1.627	4.343 Total score (0-85) Standard Error 1.470

SECONDARY outcome

Timeframe: 72 weeks

Population: The modified intent-to-treat (mITT) population, including all randomized participants who took at least one dose of the study medication and who have a baseline assessment of the primary endpoint for phase 2B (CDR-SB)

The within-participant change from baseline in NPI. The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology in Alzheimer's disease dementia based on the results of an interview with the study partner. Frequency and severity of 12 neuropsychiatric symptoms are assessed. Range: 0 to 144; higher scores indicate greater impairment.

Outcome measures

Measure	PQ912 n=17 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=23 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Change From Baseline in Neuropsychiatric Inventory (NPI)	-0.14 Total score (0-144) Standard Error 1.80	2.95 Total score (0-144) Standard Error 1.60

SECONDARY outcome

Timeframe: 76 weeks

Population: The safety (SAF) population, including all participants who had received at least one dose of the study medication

Longer-term safety and tolerability of PQ912 compared between the active and placebo arm as measured by rates of all treatment-emergent SAEs, presented as numbers of participants with at least one SAE and percentages

Outcome measures

Measure	PQ912 n=53 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=56 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Rates of All Treatment-emergent Serious Adverse Events (SAEs)	11 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to 72 weeks

Population: The safety (SAF) population, including all participants who had received at least one dose of the study medication

Assessment of the longer-term safety and tolerability of PQ912 via the C-SSRS. The C-SSRS is an instrument designed to assess the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the corresponding assessment period. The scale includes suggested questions to elicit the type of information needed to determine if a suicide-related thought or behavior occurred.

In this study it was used to 'detect' the appearance of new suicidal ideation or behavior as either "present" or "not present". The tables reflect the total number of participants (and percentage) experiencing Any suicidality, Any suicidal ideation, Any suicidal behavior, and Any self-injurious behavior at screening and subsequent time points.

Outcome measures

Measure	PQ912 n=53 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=56 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any suicidality · Not present	50 Participants	52 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any suicidal ideation · Not present	49 Participants	56 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any suicidal behavior · Not present	53 Participants	56 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any suicidality · Present	2 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any suicidal behavior · Not present	42 Participants	44 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any self-injurious behavior · Not present	42 Participants	44 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any suicidality · Present	0 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any suicidality · Not present	35 Participants	36 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any suicidal ideation · Present	0 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any suicidal ideation · Not present	35 Participants	36 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any suicidal behavior · Not present	35 Participants	37 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 36 - Any self-injurious behavior · Not present	35 Participants	37 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any suicidality · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any suicidality · Not present	33 Participants	33 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any suicidal ideation · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any suicidal ideation · Not present	33 Participants	33 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any suicidal behavior · Not present	33 Participants	33 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any suicidality · Present	0 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any suicidal ideation · Not present	23 Participants	27 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any suicidal behavior · Not present	23 Participants	28 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any self-injurious behavior · Not present	23 Participants	28 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any suicidality · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any suicidality · Not present	16 Participants	20 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any suicidal ideation · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any suicidal ideation · Not present	16 Participants	20 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any suicidal behavior · Not present	16 Participants	20 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 72 - Any self-injurious behavior · Not present	16 Participants	20 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any suicidal ideation · Present	3 Participants	4 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any suicidal ideation · Not present	50 Participants	52 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any suicidal behavior · Present	1 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any suicidal behavior · Not present	52 Participants	55 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any self-injurious behavior · Present	0 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any self-injurious behavior · Not present	53 Participants	55 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any suicidality · Present	4 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any suicidality · Not present	49 Participants	56 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any suicidal ideation · Present	4 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Baseline - Any self-injurious behavior · Not present	53 Participants	56 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any suicidality · Not present	49 Participants	54 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any suicidal ideation · Present	2 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any suicidal ideation · Not present	49 Participants	54 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any suicidal behavior · Not present	51 Participants	55 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 4 - Any self-injurious behavior · Not present	51 Participants	55 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any suicidality · Present	1 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any suicidality · Not present	51 Participants	50 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any suicidal ideation · Present	1 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any suicidal ideation · Not present	51 Participants	50 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any suicidal behavior · Not present	52 Participants	50 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 8 - Any self-injurious behavior · Not present	52 Participants	50 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any suicidality · Present	1 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any suicidality · Not present	46 Participants	47 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any suicidal ideation · Present	1 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any suicidal ideation · Not present	46 Participants	47 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any suicidal behavior · Not present	47 Participants	47 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 12 - Any self-injurious behavior · Not present	47 Participants	47 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any suicidality · Present	0 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any suicidality · Not present	46 Participants	44 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any suicidal ideation · Present	0 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any suicidal ideation · Not present	46 Participants	44 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any suicidal behavior · Not present	46 Participants	45 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 16 - Any self-injurious behavior · Not present	46 Participants	45 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any suicidality · Present	0 Participants	2 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any suicidality · Not present	42 Participants	42 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any suicidal ideation · Present	0 Participants	2 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any suicidal ideation · Not present	42 Participants	42 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 24 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any suicidal behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any self-injurious behavior · Present	0 Participants	0 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 48 - Any self-injurious behavior · Not present	33 Participants	33 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any suicidality · Not present	23 Participants	27 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Week 60 - Any suicidal ideation · Present	0 Participants	1 Participants
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Suicidality on the Columbia-Suicide Severity Rating Scale (C-SSRS) Screening - Any suicidality · Present	3 Participants	4 Participants

SECONDARY outcome

Timeframe: 76 weeks

Population: The safety (SAF) population, including all participants who had received at least one dose of the study medication

Longer-term safety and tolerability of PQ912 compared between the active and placebo arm as measured by rates of fatal treatment-emergent serious adverse events (SAEs), presented as numbers of participants with a treatment emergent SAE leading to death and percentages.

Outcome measures

Measure	PQ912 n=53 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=56 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Mortality Rates	2 Participants	0 Participants

SECONDARY outcome

Timeframe: 76 weeks

Population: The safety (SAF) population, including all participants who had received at least one dose of the study medication

Longer-term safety and tolerability of PQ912 compared between the active and placebo arm as measured by rates of all TEAEs, presented as numbers of participants with at least one TEAE and percentages

Outcome measures

Measure	PQ912 n=53 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=56 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Rates of All Treatment-emergent Adverse Events (TEAEs)	46 Participants	47 Participants

SECONDARY outcome

Timeframe: 76 weeks

Population: The safety (SAF) population, including all participants who had received at least one dose of the study medication

Longer-term safety and tolerability of PQ912 compared between the active and placebo arm as measured by rates of all AESIs presented as numbers of participants with at least one AESI and percentages .

Outcome measures

Measure	PQ912 n=53 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=56 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Rates of All Adverse Events of Special Interest (AESIs)	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 72 weeks

Population: The safety (SAF) population, including all participants who had received at least one dose of the study medication

Longer-term safety and tolerability of PQ912 compared between the active and placebo arm as measured by rates of drug discontinuation due to treatment-emergent adverse events (TEAEs), presented as numbers of participants with a TEAE leading to drug discontinuation and percentages.

Outcome measures

Measure	PQ912 n=53 Participants All participants received 600 mg PQ912 BID administered orally for 8 weeks after up-titration period starting with 150 mg BID	Placebo n=56 Participants All participants received placebo BID administered orally for 16 weeks
Phase 2B: Assessment of the Longer-term Safety and Tolerability of PQ912 as Measured by Drug Discontinuation Rates	6 Participants	2 Participants

Adverse Events

PQ912

Serious events: 11 serious events

Other events: 46 other events

Deaths: 2 deaths

Placebo

Serious events: 6 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Measure	PQ912 n=53 participants at risk All participants started at 150 mg BID and were up-titrated to 600 mg BID administered orally for up to 72 weeks and therefore, all data from these participants were collected as one single active Arm/Group and separation of doses is not possible. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	Placebo n=56 participants at risk All participants received matching placebo BID administered orally for up to 72 weeks Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Nervous system disorders Metabolic encephalopathy	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 2 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Nervous system disorders Hemorrhage intracranial	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Nervous system disorders Syncope	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Nervous system disorders Transient ischaemic attack	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Pneumonia	3.8% 2/53 • Number of events 2 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Sepsis	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Clostridium difficile colitis	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 2 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Bacterial sepsis	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Staphylococcal infection	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Urinary tract infection	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Urinary tract infection bacterial	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Urinary tract infection staphylococcal	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Cardiac disorders Acute myocardial infarction	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Cardiac disorders Angina pectoris	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Cardiac disorders Sinus node dysfunction	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Gastrointestinal disorders Gastric ulcer perforation	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
General disorders Adverse drug reaction	0.00% 0/53 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Injury, poisoning and procedural complications Wound evisceration	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Metabolism and nutrition disorders Hyperglycaemia	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Reproductive system and breast disorders Ovarian cyst	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	0.00% 0/56 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.

Other adverse events

Measure	PQ912 n=53 participants at risk All participants started at 150 mg BID and were up-titrated to 600 mg BID administered orally for up to 72 weeks and therefore, all data from these participants were collected as one single active Arm/Group and separation of doses is not possible. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	Placebo n=56 participants at risk All participants received matching placebo BID administered orally for up to 72 weeks Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations COVID-19	9.4% 5/53 • Number of events 5 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	7.1% 4/56 • Number of events 5 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Nasopharyingitis	7.5% 4/53 • Number of events 4 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	3.6% 2/56 • Number of events 2 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Infections and infestations Urinary tract infection	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	7.1% 4/56 • Number of events 7 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Gastrointestinal disorders Diarrhoea	17.0% 9/53 • Number of events 9 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	8.9% 5/56 • Number of events 6 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Gastrointestinal disorders Nausea	7.5% 4/53 • Number of events 4 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	7.1% 4/56 • Number of events 4 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Injury, poisoning and procedural complications Fall	15.1% 8/53 • Number of events 12 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	12.5% 7/56 • Number of events 11 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Injury, poisoning and procedural complications Skin laceration	3.8% 2/53 • Number of events 2 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	5.4% 3/56 • Number of events 4 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Injury, poisoning and procedural complications Contusion	3.8% 2/53 • Number of events 2 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	5.4% 3/56 • Number of events 3 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Injury, poisoning and procedural complications Skin abrasion	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	5.4% 3/56 • Number of events 3 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Psychiatric disorders Depression	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	5.4% 3/56 • Number of events 3 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Investigations Alanine aminotransferase increased	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	5.4% 3/56 • Number of events 3 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Investigations Blood creatine phosphokinase increased	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	5.4% 3/56 • Number of events 3 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Nervous system disorders Headache	3.8% 2/53 • Number of events 2 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	7.1% 4/56 • Number of events 5 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Nervous system disorders Dizziness	1.9% 1/53 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	8.9% 5/56 • Number of events 5 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.
Musculoskeletal and connective tissue disorders Back pain	11.3% 6/53 • Number of events 6 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.	1.8% 1/56 • Number of events 1 • 76 weeks All participants started at 150 mg BID and were up-titrated to 600 mg BID. As safety data were collected continuously across titration, separation of doses is not possible. Therefore, safety data are reported as one single active Arm/Group. Participants enrolled in Phase 2A remained in the study for seamless inclusion in the Phase 2B evaluation (up to 72 weeks). No new participants were enrolled in Phase 2B.

Additional Information

Study Director

Vivoryon Therapeutics N.V.

Phone: 0049 34555599

Email: clinics@vivoryon.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60