Trial Outcomes & Findings for Safety and Efficacy of Piromelatine in Mild Alzheimer's Disease Patients (ReCOGNITION) (NCT NCT02615002)

NCT ID: NCT02615002

Last Updated: 2024-07-05

Results Overview

The global composite score of the cNTB combines the International Shopping List Test (ISLT), One Card Learning (OCL), Identification (IDN), Detection (DET), One Back Card (OBK), Controlled Oral Word Association Test (COWAT), and the Categorical Fluency Test (CFT). For each test, a z-score relative to the study baseline is calculated. The cNTB global composite score is the mean of all z-scores from the tests listed above. The scale range is from -3 to 3. Zero Z-score means no cognitive change. A negative value means decline, while a positive value means improvement.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 371 participants
• Primary outcome timeframe: 26 weeks
• Results posted on: 2024-07-05

Participant Flow

The first period of the study consisted of a run-in phase where all participants received Placebo, followed by a second period where participants were randomized to "Piromelatine 5mg", "Piromelatine 20mg", "Piromelatine 50mg", or "Placebo" Arm/Groups for the dose escalation phase.

Participant milestones

Measure	Experimental: Piromelatine 5 mg Run-In placebo (2 weeks), followed by 5 mg Piromelatine once daily (26 weeks)	Experimental: Piromelatine 20 mg Run-In placebo (2 weeks), followed by 20 mg Piromelatine once daily (26 weeks).	Experimental: Piromelatine 50 mg Run-In placebo (2 weeks), followed by 50 mg Piromelatine once daily (26 weeks).	Placebo Comparator Run-In placebo (2 weeks), followed by Placebo control once daily (26 weeks).
Run-In Phase (2 Weeks) STARTED	89	88	88	106
Run-In Phase (2 Weeks) COMPLETED	89	88	88	106
Run-In Phase (2 Weeks) NOT COMPLETED	0	0	0	0
Double Blind Dose Escalation (26 Weeks) STARTED	89	88	88	106
Double Blind Dose Escalation (26 Weeks) Number of Baseline Participants	83	87	80	102
Double Blind Dose Escalation (26 Weeks) COMPLETED	71	88	88	85
Double Blind Dose Escalation (26 Weeks) NOT COMPLETED	18	0	0	21

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of Piromelatine in Mild Alzheimer's Disease Patients (ReCOGNITION)

Baseline characteristics by cohort

Measure	Experimental: Piromelatine 5 mg n=83 Participants Piromelatine 5 mg tablet once daily	Experimental: Piromelatine 20 mg n=87 Participants Piromelatine 20 mg tablet once daily	Experimental: Piromelatine 50 mg n=80 Participants Piromelatine 50 mg tablet once daily	Placebo Comparator: Placebo n=102 Participants Placebo tablet given once daily	Total n=352 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical >=65 years	83 Participants n=5 Participants	87 Participants n=7 Participants	80 Participants n=5 Participants	102 Participants n=4 Participants	352 Participants n=21 Participants
Age, Continuous	73.1 years STANDARD_DEVIATION 6.65 • n=5 Participants	72.7 years STANDARD_DEVIATION 7.97 • n=7 Participants	73.3 years STANDARD_DEVIATION 6.62 • n=5 Participants	73.3 years STANDARD_DEVIATION 7.11 • n=4 Participants	73.1 years STANDARD_DEVIATION 7.10 • n=21 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	49 Participants n=7 Participants	49 Participants n=5 Participants	58 Participants n=4 Participants	200 Participants n=21 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	38 Participants n=7 Participants	31 Participants n=5 Participants	44 Participants n=4 Participants	152 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	21 Participants n=7 Participants	24 Participants n=5 Participants	20 Participants n=4 Participants	83 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	65 Participants n=5 Participants	66 Participants n=7 Participants	56 Participants n=5 Participants	82 Participants n=4 Participants	269 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	11 Participants n=5 Participants	9 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	34 Participants n=21 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants	78 Participants n=7 Participants	72 Participants n=5 Participants	92 Participants n=4 Participants	312 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	83 participants n=5 Participants	87 participants n=7 Participants	80 participants n=5 Participants	102 participants n=4 Participants	352 participants n=21 Participants

PRIMARY outcome

Timeframe: 26 weeks

The global composite score of the cNTB combines the International Shopping List Test (ISLT), One Card Learning (OCL), Identification (IDN), Detection (DET), One Back Card (OBK), Controlled Oral Word Association Test (COWAT), and the Categorical Fluency Test (CFT). For each test, a z-score relative to the study baseline is calculated.

The cNTB global composite score is the mean of all z-scores from the tests listed above.

The scale range is from -3 to 3. Zero Z-score means no cognitive change. A negative value means decline, while a positive value means improvement.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Computerized Neuropsychological Test Battery (cNTB) Z-Scores - Change From Baseline	0.0434 z-score Interval -0.0728 to 0.1391	0.1175 z-score Interval 0.0121 to 0.2153	0.0297 z-score Interval -0.09 to 0.1247	0.0591 z-score Interval -0.0435 to 0.1483

SECONDARY outcome

Timeframe: 13 weeks, and 26 weeks

The Change From Baseline in Global Impression of Change (CGIC) rating is made on a 7-point Likert-type scale where the change from baseline is rated as marked improvement (1), moderate improvement (2), minimal improvement (3), no change (4), minimal worsening (5), moderate worsening (6), marked worsening (7).

Mean values at 13 and 26 weeks are relative to baseline.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Change From Baseline in Global Impression of Change (CGIC) 13 weeks	3.93 score on a scale Standard Deviation 0.88	3.95 score on a scale Standard Deviation 0.78	3.87 score on a scale Standard Deviation 0.92	3.89 score on a scale Standard Deviation 0.80
Change From Baseline in Global Impression of Change (CGIC) 26 weeks	4.13 score on a scale Standard Deviation 1.07	3.94 score on a scale Standard Deviation 1.02	3.87 score on a scale Standard Deviation 0.98	3.99 score on a scale Standard Deviation 1.01

SECONDARY outcome

Timeframe: Baseline, 13 weeks, and 26 weeks

ADCS-MCI-ADL is an evaluation scale with information provided by an informant/caregiver to describe the functional impairment of patients with mild cognitive impairment (MCI).

The ADCS-ADL is a 23-item scale that includes 6 basic ADLs (BADLs) and 17 Instrumental Activities of Daily Living (IADLs) that provide a total score of 0-78, with a lower score indicating greater severity, meaning a worse outcome.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for MCI (Mild Cognitive Impairment) Patients (ADCS-MCI-ADL) Baseline	40.7 score on a scale Standard Deviation 6.73	38.4 score on a scale Standard Deviation 8.98	39.2 score on a scale Standard Deviation 7.60	39.4 score on a scale Standard Deviation 8.60
Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for MCI (Mild Cognitive Impairment) Patients (ADCS-MCI-ADL) 13 weeks	40.4 score on a scale Standard Deviation 6.72	39.6 score on a scale Standard Deviation 8.89	39.1 score on a scale Standard Deviation 8.81	39.5 score on a scale Standard Deviation 8.06
Alzheimer's Disease Cooperative Study/Activities of Daily Living Scale Adapted for MCI (Mild Cognitive Impairment) Patients (ADCS-MCI-ADL) 26 weeks	40.6 score on a scale Standard Deviation 6.59	39.3 score on a scale Standard Deviation 9.11	39.8 score on a scale Standard Deviation 7.94	40.4 score on a scale Standard Deviation 8.07

SECONDARY outcome

Timeframe: Baseline, 13 weeks, and 26 weeks

The ADAS was designed to measure the severity of the most important symptoms of AD. Its subscale, ADAS-cog, is the most popular cognitive testing instrument used in clinical trials, measuring the disturbances of memory, language, praxis, attention, and other cognitive abilities that are often referred to as the core symptoms of AD.

ADAS-cog14 comprises 14 items summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog14) Baseline	26.1 score on a scale Standard Deviation 7.72	26.3 score on a scale Standard Deviation 9.16	26.4 score on a scale Standard Deviation 7.91	26.6 score on a scale Standard Deviation 8.62
Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog14) 13 weeks	25.1 score on a scale Standard Deviation 8.39	26.7 score on a scale Standard Deviation 9.37	25.5 score on a scale Standard Deviation 10.01	26.6 score on a scale Standard Deviation 9.87
Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog14) 26 weeks	25.3 score on a scale Standard Deviation 8.93	26.0 score on a scale Standard Deviation 10.12	24.9 score on a scale Standard Deviation 9.35	25.2 score on a scale Standard Deviation 9.97

SECONDARY outcome

Timeframe: Baseline, and 26 weeks

Systolic and Diastolic Blood Pressure is followed during the study, as safety and tolerability measures.

Changes in BP following treatment, leading to values out of the normal limits mean a worse outcome.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Safety and Tolerability - Blood Pressure (mmHg) Systolic BP - Baseline	128.7 mmHg Standard Deviation 14.51	130.8 mmHg Standard Deviation 13.19	128.5 mmHg Standard Deviation 11.35	132.3 mmHg Standard Deviation 15.13
Safety and Tolerability - Blood Pressure (mmHg) Diastolic BP - Baseline	75.3 mmHg Standard Deviation 9.15	76.5 mmHg Standard Deviation 8.37	76.3 mmHg Standard Deviation 7.57	76.3 mmHg Standard Deviation 8.26
Safety and Tolerability - Blood Pressure (mmHg) Diastolic BP - 26 weeeks	76.3 mmHg Standard Deviation 8.48	76.2 mmHg Standard Deviation 8.47	77.3 mmHg Standard Deviation 8.78	76.3 mmHg Standard Deviation 8.52
Safety and Tolerability - Blood Pressure (mmHg) Systolic BP - 26 weeks	131.9 mmHg Standard Deviation 13.61	132.4 mmHg Standard Deviation 12.31	129.9 mmHg Standard Deviation 10.01	131.5 mmHg Standard Deviation 12.93

SECONDARY outcome

Timeframe: Baseline, and 26 weeks

Heart Rate within normal limits = 60-100 beats per minute (bpm) during the study means a good outcome in terms of safety.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Safety and Tolerability - Heart Rate (Bpm) Heart rate - baseline	68.1 bpm Standard Deviation 10.67	68.7 bpm Standard Deviation 9.44	69.6 bpm Standard Deviation 9.55	67.2 bpm Standard Deviation 9.68
Safety and Tolerability - Heart Rate (Bpm) Heart rate - 26 weeks	65.9 bpm Standard Deviation 9.89	67.0 bpm Standard Deviation 9.95	66.9 bpm Standard Deviation 9.28	67.9 bpm Standard Deviation 10.13

SECONDARY outcome

Timeframe: Baseline, and 26 weeks

QT interval corrected for heart rate by Fridericia's cube root formula (QTcF). The QTc is considered normal at < 450 msec in males, and < 470 msec in females.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Safety and Tolerability - ECG Interval Results - QTcF (Msec) Baseline	417.1 msec Standard Deviation 24.16	416.4 msec Standard Deviation 34.97	413.9 msec Standard Deviation 50.48	416.5 msec Standard Deviation 20.57
Safety and Tolerability - ECG Interval Results - QTcF (Msec) 26 weeks	414.3 msec Standard Deviation 27.29	421.2 msec Standard Deviation 24.86	416.6 msec Standard Deviation 24.87	408.9 msec Standard Deviation 54.47

SECONDARY outcome

Timeframe: Baseline, and 26 weeks

Hematology (GI/L).

1 gill (GI) = 0.118294118 liter (L). No major changes or shifts from baseline mean good safety and tolerability.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Safety and Tolerability - Hematology Basophils - baseline	0.050 GI/L Standard Deviation 0.0141	0.070 GI/L Standard Deviation 0.0141	0.067 GI/L Standard Deviation 0.0153	0.063 GI/L Standard Deviation 0.0153
Safety and Tolerability - Hematology Basophils - 26 weeks	0.080 GI/L Standard Deviation 0	0.050 GI/L Standard Deviation 0	0.050 GI/L Standard Deviation 0.0141	0.080 GI/L Standard Deviation 0.0283
Safety and Tolerability - Hematology Eosinophils - baseline	0.290 GI/L Standard Deviation 0.0990	0.215 GI/L Standard Deviation 0.0354	0.110 GI/L Standard Deviation 0.0693	0.153 GI/L Standard Deviation 0.0208
Safety and Tolerability - Hematology Eosinophils - 26 weeks	0.170 GI/L Standard Deviation 0	0.180 GI/L Standard Deviation 0	0.130 GI/L Standard Deviation 0.0283	0.250 GI/L Standard Deviation 0.0283
Safety and Tolerability - Hematology Leukocytes - baseline	6.455 GI/L Standard Deviation 1.5768	8.715 GI/L Standard Deviation 2.7224	6.140 GI/L Standard Deviation 0.6940	5.407 GI/L Standard Deviation 0.8755
Safety and Tolerability - Hematology Leukocytes - 26 weeks	5.210 GI/L Standard Deviation 0	10.050 GI/L Standard Deviation 0	5.885 GI/L Standard Deviation 0.3465	6.970 GI/L Standard Deviation 0.9617
Safety and Tolerability - Hematology Lymphocytes - baseline (GI/L)	1.605 GI/L Standard Deviation 0.7425	2.535 GI/L Standard Deviation 0.0071	1.943 GI/L Standard Deviation 0.2397	1.363 GI/L Standard Deviation 0.3320
Safety and Tolerability - Hematology Lymphocytes - 26 weeks	0.920 GI/L Standard Deviation 0	2.370 GI/L Standard Deviation 0	1.805 GI/L Standard Deviation 0.3182	2.085 GI/L Standard Deviation 1.3223
Safety and Tolerability - Hematology Monocytes - baseline	0.510 GI/L Standard Deviation 0.2828	0.405 GI/L Standard Deviation 0.0919	0.357 GI/L Standard Deviation 0.1102	0.347 GI/L Standard Deviation 0.0611
Safety and Tolerability - Hematology Monocytes - 26 weeks	0.450 GI/L Standard Deviation 0	0.700 GI/L Standard Deviation 0	0.370 GI/L Standard Deviation 0.0141	0.345 GI/L Standard Deviation 0.0495
Safety and Tolerability - Hematology Neutrophils - baseline	3.990 GI/L Standard Deviation 0.4525	5.495 GI/L Standard Deviation 2.6658	3.660 GI/L Standard Deviation 0.2905	3.483 GI/L Standard Deviation 1.1801
Safety and Tolerability - Hematology Neutrophils - 26 weeks	3.600 GI/L Standard Deviation 0	6.750 GI/L Standard Deviation 0	3.525 GI/L Standard Deviation 0.0071	4.205 GI/L Standard Deviation 0.3041
Safety and Tolerability - Hematology Platelets - baseline	238.5 GI/L Standard Deviation 84.15	299.0 GI/L Standard Deviation 2.83	241.0 GI/L Standard Deviation 46.13	167.3 GI/L Standard Deviation 26.95
Safety and Tolerability - Hematology Platelets - 26 weeks	144.0 GI/L Standard Deviation 0	301.0 GI/L Standard Deviation 0	223.0 GI/L Standard Deviation 48.08	283.0 GI/L Standard Deviation 111.72

SECONDARY outcome

Timeframe: Baseline, and 26 weeks

Blood Chemistry follow-up during the experiment. No major changes or shifts from baseline mean good safety and tolerability.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Safety and Tolerability - Blood Chemistry (mmol/L) Sodium - baseline	140.5 mmol/L Standard Deviation 2.12	141.5 mmol/L Standard Deviation 0.71	139.3 mmol/L Standard Deviation 2.31	139.0 mmol/L Standard Deviation 1.73
Safety and Tolerability - Blood Chemistry (mmol/L) Sodium -26 weeks	135.0 mmol/L Standard Deviation 0	141.0 mmol/L Standard Deviation 0	143.0 mmol/L Standard Deviation 2.83	140.0 mmol/L Standard Deviation 1.41
Safety and Tolerability - Blood Chemistry (mmol/L) Urea Nitrogen - baseline	7.35 mmol/L Standard Deviation 0.778	7.70 mmol/L Standard Deviation 3.818	5.00 mmol/L Standard Deviation 0.400	5.00 mmol/L Standard Deviation 1.212
Safety and Tolerability - Blood Chemistry (mmol/L) Urea Nitrogen - 26 weeks	8.20 mmol/L Standard Deviation 0	5.70 mmol/L Standard Deviation 0	5.35 mmol/L Standard Deviation 0.495	4.50 mmol/L Standard Deviation 1.273
Safety and Tolerability - Blood Chemistry (mmol/L) Glucose - baseline	5.89 mmol/L Standard Deviation 1.883	5.97 mmol/L Standard Deviation 2.045	5.51 mmol/L Standard Deviation 1.322	5.78 mmol/L Standard Deviation 1.598
Safety and Tolerability - Blood Chemistry (mmol/L) Glucose - 26 weeks	5.86 mmol/L Standard Deviation 1.770	6.25 mmol/L Standard Deviation 2.121	5.99 mmol/L Standard Deviation 2.351	5.80 mmol/L Standard Deviation 1.461
Safety and Tolerability - Blood Chemistry (mmol/L) Calcium - baseline	2.385 mmol/L Standard Deviation 0.1626	2.470 mmol/L Standard Deviation 0.0707	2.307 mmol/L Standard Deviation 0.1007	2.363 mmol/L Standard Deviation 0.1290
Safety and Tolerability - Blood Chemistry (mmol/L) Calcium - 26 weeks	2.270 mmol/L Standard Deviation 0	2.370 mmol/L Standard Deviation 0	2.300 mmol/L Standard Deviation 0	2.335 mmol/L Standard Deviation 0.0495

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, and 26 weeks

The NPI scale consists of 12 domains that are rated for both frequency (range 1 to 4) and severity (range 1 to 3). A composite score for each domain is calculated (frequency × severity), and it ranges from 1 to 12.

For each item, there is a leading question. If the symptom is absent, then the frequency, severity, and distress scores are not completed. In this case, the score is 0 for the item. The sum of the composite scores yields the NPI total score (1-12).

A negative change in the score indicates an improvement from baseline (symptom reduction).

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
NeuroPsychiatric Inventory (NPI) Total Score Baseline	11.2 NPI total score Standard Deviation 10.30	10.3 NPI total score Standard Deviation 8.39	12.0 NPI total score Standard Deviation 8.75	10.8 NPI total score Standard Deviation 10.13
NeuroPsychiatric Inventory (NPI) Total Score 26 weeks	11.4 NPI total score Standard Deviation 11.60	9.0 NPI total score Standard Deviation 7.85	11.9 NPI total score Standard Deviation 10.66	9.8 NPI total score Standard Deviation 10.34

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, 4 weeks, 13 weeks, 26 weeks

PSQI is an effective instrument used to measure the quality and patterns of sleep in older adults.

It differentiates "poor" from "good" sleep by measuring 7 areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction over the last month.

PSQI includes seven components, each scored 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality.

Outcome measures

Measure	Piromelatine 5 mg n=83 Participants 5 mg Piromelatine tablets once daily	Piromelatine 20 mg n=87 Participants 20 mg Piromelatine tablets once daily	Piromelatine 50 mg n=80 Participants 50 mg Piromelatine tablets once daily	Placebo Comparator n=102 Participants Placebo tablet once daily
Pittsburgh Sleep Quality Index (PSQI) - Global Component Score Baseline	6.8 PSQI global score Standard Deviation 4.39	5.9 PSQI global score Standard Deviation 3.99	6.0 PSQI global score Standard Deviation 4.14	5.6 PSQI global score Standard Deviation 3.66
Pittsburgh Sleep Quality Index (PSQI) - Global Component Score 4 weeks	5.8 PSQI global score Standard Deviation 3.97	5.4 PSQI global score Standard Deviation 3.36	5.4 PSQI global score Standard Deviation 3.56	5.6 PSQI global score Standard Deviation 3.39
Pittsburgh Sleep Quality Index (PSQI) - Global Component Score 13 weeks	6.2 PSQI global score Standard Deviation 3.85	5.2 PSQI global score Standard Deviation 3.04	5.5 PSQI global score Standard Deviation 3.20	5.1 PSQI global score Standard Deviation 3.11
Pittsburgh Sleep Quality Index (PSQI) - Global Component Score 26 weeks	5.7 PSQI global score Standard Deviation 3.62	4.7 PSQI global score Standard Deviation 3.26	5.2 PSQI global score Standard Deviation 3.21	5.1 PSQI global score Standard Deviation 3.68

Adverse Events

Piromelatine 5 mg

Serious events: 2 serious events

Other events: 12 other events

Deaths: 1 deaths

Piromelatine 20 mg

Serious events: 6 serious events

Other events: 14 other events

Deaths: 0 deaths

Piromelatine 50 mg

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo Comparator

Serious events: 6 serious events

Other events: 29 other events

Deaths: 0 deaths

Run-In Phase

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Piromelatine 5 mg n=88 participants at risk 5 mg Piromelatine tablets once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Piromelatine 20 mg n=88 participants at risk 20 mg Piromelatine tablets once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Piromelatine 50 mg n=87 participants at risk 50 mg Piromelatine tablets once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Placebo Comparator n=105 participants at risk Placebo tablet once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Run-In Phase n=368 participants at risk Placebo tablet once daily for 2 weeks, intended to assess eligibility before starting the dose escalation phase (Weeks 0-2).
Musculoskeletal and connective tissue disorders Humerus Fracture	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.9% 2/105 • Number of events 3 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Renal and urinary disorders Kidney Infection	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Injury, poisoning and procedural complications Head Injury	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Injury, poisoning and procedural complications Fall	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Cardiac disorders Ischaemic cardiomyopathy	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Duodenal ulcer	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Duodenitis	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Gastritis erosive	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Colitis	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Cardiac disorders Acute myocardial infarction	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Musculoskeletal and connective tissue disorders Femur Fracture	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Cardiac disorders Bradycardia	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Cardiac disorders Cardio-respiratory Arrest	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Cardiac disorders Ischemic Cardiopathy	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
General disorders Syncope	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Cardiac disorders Transient ischaemic attack	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Blood and lymphatic system disorders Anaemia	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
General disorders Multi-organ disorder	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Anxiety	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).

Other adverse events

Measure	Piromelatine 5 mg n=88 participants at risk 5 mg Piromelatine tablets once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Piromelatine 20 mg n=88 participants at risk 20 mg Piromelatine tablets once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Piromelatine 50 mg n=87 participants at risk 50 mg Piromelatine tablets once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Placebo Comparator n=105 participants at risk Placebo tablet once daily for 26 weeks (Dose Escalation Phase = Weeks 2-28).	Run-In Phase n=368 participants at risk Placebo tablet once daily for 2 weeks, intended to assess eligibility before starting the dose escalation phase (Weeks 0-2).
Nervous system disorders Headache	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	3.4% 3/88 • Number of events 6 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	7.6% 8/105 • Number of events 15 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Abnormal dreams	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	3.4% 3/87 • Number of events 3 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.9% 2/105 • Number of events 2 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Nervous system disorders Dizziness	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	3.8% 4/105 • Number of events 4 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Nervous system disorders Somnolence	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.9% 2/105 • Number of events 2 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Nervous system disorders Head discomfort	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Nervous system disorders Hypersomnia	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Nervous system disorders Sedation	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Insomnia	2.3% 2/88 • Number of events 2 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Agitation	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.9% 2/105 • Number of events 2 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Initial insomnia	2.3% 2/88 • Number of events 2 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Disorientation	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Disturbance in sexual arousal	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Hallucination	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Psychiatric disorders Libido increased	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Nausea	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	2.3% 2/88 • Number of events 3 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	2.9% 3/105 • Number of events 5 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Constipation	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	2.9% 3/105 • Number of events 5 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Diarrhoea	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Large intestine polyp	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 2 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Abdominal distension	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Abdominal pain	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Dry mouth	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Dyspepsia	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Gastrointestinal disorders Gastrooesophageal reflux	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Infections and infestations Nasopharyngitis	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	2.3% 2/88 • Number of events 3 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Infections and infestations Kidney infection	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Infections and infestations Sinusitis	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Infections and infestations Upper respiratory tract infection	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Infections and infestations Influenza	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Infections and infestations Staphylococcal infection	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Infections and infestations Tubo-ovarian abscess	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.95% 1/105 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Skin and subcutaneous tissue disorders Rash	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Injury, poisoning and procedural complications Fall	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/87 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.9% 2/105 • Number of events 2 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/88 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).
General disorders Asthenia	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/88 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	1.1% 1/87 • Number of events 1 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/105 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).	0.00% 0/368 • 28 weeks (2 weeks Run-In Phase + 26 weeks Dose Escalation Phase) The data presented includes adverse events from the Run-In Phase (2 weeks of placebo, intended to assess eligibility into the dose escalation study), and the Dose Escalation Phase (26 weeks of treatment with investigational drug versus placebo).

Additional Information

Tali Nir, DVM, VP Clinical and Regulatory Affairs

Neurim Pharmaceuticals

Phone: +972-3-7684902

Email: talin@neurim.com

Results disclosure agreements

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