Trial Outcomes & Findings for Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis (NCT NCT00811395)

NCT ID: NCT00811395

Last Updated: 2012-12-31

Results Overview

AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 182 participants
• Primary outcome timeframe: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
• Results posted on: 2012-12-31

Participant Flow

107 and 110 participants who successfully completed 24-week visit in, respectively, PDY6045 and PDY6046 studies, were offered to continue their treatment in this extension study. After signature of the informed consent and confirmation of selection criteria, 86 and 96 participants entered the extension study.

An Interactive Voice Response System was used to allocate kits containing the same treatment as in the initial study. Analysis included all participants randomized in the initial studies and all data collected from randomization according to intent-to-treat principal.

Participant milestones

Measure	Placebo + IFN-β Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Initial Treatment (PDY6045 or PDY6046) STARTED	41	37	38	40	42	41
Initial Treatment (PDY6045 or PDY6046) COMPLETED	38	33	36	38	37	35
Initial Treatment (PDY6045 or PDY6046) NOT COMPLETED	3	4	2	2	5	6
Extension Treatment STARTED	31	28	27	37	30	29
Extension Treatment COMPLETED	29	22	24	34	30	27
Extension Treatment NOT COMPLETED	2	6	3	3	0	2

Reasons for withdrawal

Measure	Placebo + IFN-β Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Extension Treatment Adverse Event	1	2	2	2	0	1
Extension Treatment Progressive disease	1	1	0	0	0	0
Extension Treatment Participant did not wish to continue	0	3	0	1	0	1
Extension Treatment Other than above	0	0	1	0	0	0

Baseline Characteristics

Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis

Baseline characteristics by cohort

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=40 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=41 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Total n=239 Participants Total of all reporting groups
Age, Customized <38 years	17 participants n=5 Participants	9 participants n=7 Participants	15 participants n=5 Participants	11 participants n=4 Participants	12 participants n=21 Participants	13 participants n=10 Participants	77 participants n=115 Participants
Age, Customized >=38 years	24 participants n=5 Participants	28 participants n=7 Participants	23 participants n=5 Participants	29 participants n=4 Participants	30 participants n=21 Participants	28 participants n=10 Participants	162 participants n=115 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	25 Participants n=7 Participants	25 Participants n=5 Participants	31 Participants n=4 Participants	33 Participants n=21 Participants	33 Participants n=10 Participants	178 Participants n=115 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	9 Participants n=4 Participants	9 Participants n=21 Participants	8 Participants n=10 Participants	61 Participants n=115 Participants
Region of Enrollment Europe	28 participants n=5 Participants	25 participants n=7 Participants	24 participants n=5 Participants	22 participants n=4 Participants	22 participants n=21 Participants	22 participants n=10 Participants	143 participants n=115 Participants
Region of Enrollment North America	13 participants n=5 Participants	12 participants n=7 Participants	14 participants n=5 Participants	18 participants n=4 Participants	20 participants n=21 Participants	19 participants n=10 Participants	96 participants n=115 Participants

PRIMARY outcome

Timeframe: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=40 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=41 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Overview of Adverse Events [AE] Any AE	35 participants	35 participants	33 participants	39 participants	40 participants	38 participants
Overview of Adverse Events [AE] - serious AE	2 participants	4 participants	1 participants	6 participants	5 participants	2 participants
Overview of Adverse Events [AE] - AE leading to death	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Overview of Adverse Events [AE] - AE leading to study drug discontinuation	2 participants	3 participants	3 participants	2 participants	3 participants	5 participants

PRIMARY outcome

Timeframe: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

AE with potential risk of occurrence were defined as follows:

• Hepatic disorders;
• Immune effects, mainly effects on bone marrow and infection;
• Pancreatic disorders;
• Malignancy;
• Skin disorders, mainly hair loss and hair thinning;
• Pulmonary disorders;
• Hypertension;
• Peripheral neuropathy;
• Psychiatric disorders;
• Hypersensitivity.

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=40 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=41 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Overview of AE With Potential Risk of Occurence Any AE with potential risk of occurence	28 participants	30 participants	30 participants	34 participants	33 participants	32 participants
Overview of AE With Potential Risk of Occurence - Hepatic disorder AE	7 participants	11 participants	13 participants	5 participants	4 participants	5 participants
Overview of AE With Potential Risk of Occurence - Pancreatic disorder AE	8 participants	5 participants	11 participants	6 participants	6 participants	11 participants
Overview of AE With Potential Risk of Occurence - Malignancy AE	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Overview of AE With Potential Risk of Occurence - Hair loss / hair thinning AE	1 participants	3 participants	4 participants	1 participants	5 participants	7 participants
Overview of AE With Potential Risk of Occurence - Pulmonary disorder AE	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants
Overview of AE With Potential Risk of Occurence - Hypertension-related AE	1 participants	4 participants	6 participants	0 participants	2 participants	2 participants
Overview of AE With Potential Risk of Occurence - Peripheral neuropathy AE	5 participants	3 participants	4 participants	4 participants	5 participants	10 participants
Overview of AE With Potential Risk of Occurence - Psychiatric disorder AE	1 participants	1 participants	2 participants	3 participants	3 participants	1 participants
Overview of AE With Potential Risk of Occurence - Hypersensitivity AE	6 participants	4 participants	4 participants	4 participants	6 participants	10 participants
Overview of AE With Potential Risk of Occurence - Immune effects related AE	16 participants	21 participants	20 participants	27 participants	22 participants	21 participants

PRIMARY outcome

Timeframe: from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.

Hepatic parameters thresholds were defined as follows:

• Alanine Aminotransferase [ALT] >3, 5, 10 or 20 Upper Normal Limit [ULN];
• Aspartate aminotransferase [AST] >3, 5, 10 or 20 ULN;
• Alkaline Phosphatase >1.5 ULN;
• Total Bilirubin [TB] >1.5 or 2 ULN;
• ALT >3 ULN and TB >2 ULN;

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=40 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=41 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] ALT >3 ULN	2 participants	1 participants	3 participants	1 participants	0 participants	1 participants
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] - ALT >5 ULN	1 participants	0 participants	1 participants	1 participants	0 participants	1 participants
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] - ALT >10 ULN	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] AST >3 ULN	1 participants	0 participants	1 participants	1 participants	0 participants	0 participants
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] - AST >5 ULN	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] Alkaline Phosphatase >1.5 ULN	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] TB >1.5 ULN	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] ALT >3 ULN and TB >2 ULN	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.

Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale [EDSS] score or Functional System scores.

To account for the different treatment durations among participants, two Poisson regression models with robust error variance were used (total number of confirmed relapses as response variable, log-transformed treatment duration as "offset" variable and:

• Model 1 (IFN-β groups): treatment group, region of enrollment and IFN-β dose level as covariates
• Model 2 (GA groups): treatment group and region of enrollment as covariates)

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=41 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=40 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Annualized Relapse Rate [ARR]: Poisson Regression Estimates	0.343 relapses per year Interval 0.162 to 0.727	0.231 relapses per year Interval 0.101 to 0.529	0.144 relapses per year Interval 0.065 to 0.318	0.420 relapses per year Interval 0.27 to 0.654	0.262 relapses per year Interval 0.14 to 0.489	0.497 relapses per year Interval 0.316 to 0.783

SECONDARY outcome

Timeframe: 48 weeks

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

12-week sustained disability progression was defined as an increase from baseline of at least 1-point in EDSS score (at least 0.5-point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks.

If no disability progression was observed on or before last EDSS evaluation before study drug discontinuation, then the participant was considered as free of disability progression.

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=41 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=40 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Overview of 12-week Sustained Disability Progression Disability progression	0 participants Interval 0.0 to 0.0	3 participants Interval 0.0 to 8.9	2 participants Interval 0.0 to 7.9	4 participants Interval 0.0 to 7.3	1 participants Interval 0.0 to 0.0	4 participants Interval 0.0 to 13.2
Overview of 12-week Sustained Disability Progression Free of disability progression	40 participants Interval 0.0 to 0.0	33 participants Interval 0.0 to 23.1	36 participants Interval 0.0 to 15.2	37 participants Interval 0.7 to 20.4	41 participants Interval 0.0 to 9.8	36 participants Interval 1.0 to 24.6

SECONDARY outcome

Timeframe: 48 weeks

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

Probability of disability progression at 24 and 48 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase. Participants free of disability progression were censored at the date of the last on-treatment EDSS evaluation.

Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=41 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=40 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints Probability of disability progression at 24 weeks	0.0 percent probability Interval 0.0 to 0.0	3.0 percent probability Interval 0.0 to 8.9	2.7 percent probability Interval 0.0 to 7.9	2.5 percent probability Interval 0.0 to 7.3	0.0 percent probability Interval 0.0 to 0.0	5.6 percent probability Interval 0.0 to 13.2
Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints Probability of disability progression at 48 weeks	0.0 percent probability Interval 0.0 to 0.0	11.1 percent probability Interval 0.0 to 23.1	6.4 percent probability Interval 0.0 to 15.2	10.6 percent probability Interval 0.7 to 20.4	3.3 percent probability Interval 0.0 to 9.8	12.8 percent probability Interval 1.0 to 24.6

SECONDARY outcome

Timeframe: baseline (before randomization in PDY6045 or PDY6046) and 48 weeks

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis.

Least-square means were estimated using two Mixed-effect models with repeated measures [MMRM] on cubic root transformed volume data:

• Model 1 (IFN-β groups): treatment group, region of enrollment, IFN-β dose level, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors;
• Model 2 (GA groups): treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors.

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=41 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=40 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)	-0.017 mililiters (mL) Standard Error 0.028 • Interval -11.29 to 7.26	-0.011 mililiters (mL) Standard Error 0.030 • Interval -9.63 to 3.35	-0.012 mililiters (mL) Standard Error 0.029 • Interval -8.97 to 7.29	0.016 mililiters (mL) Standard Error 0.036 • Interval -15.62 to 19.44	-0.010 mililiters (mL) Standard Error 0.037 • Interval -15.91 to 7.04	-0.063 mililiters (mL) Standard Error 0.039 • Interval -10.69 to 7.02

SECONDARY outcome

Timeframe: 48 weeks

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.

To account for the different number of scans among participants, two Poisson regression models with robust error variance were used (total number of Gd-enhancing T1-lesions as response variable, log-transformed number of scans as "offset" variable and:

• Model 1 (IFN-β groups): Treatment group, region of enrollment, IFN-β dose level and baseline number of Gd-enhancing T1-lesions as covariates
• Model 2 (GA groups): Treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates)

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=41 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=40 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)	0.521 lesions per scan Interval 0.318 to 0.854	0.080 lesions per scan Interval 0.032 to 0.204	0.090 lesions per scan Interval 0.052 to 0.154	0.333 lesions per scan Interval 0.171 to 0.649	0.120 lesions per scan Interval 0.059 to 0.243	0.178 lesions per scan Interval 0.098 to 0.324

SECONDARY outcome

Timeframe: 48 weeks

Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.

Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.

Outcome measures

Measure	Placebo + IFN-β n=41 Participants Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 Participants Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 Participants Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=41 Participants Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 7 mg + GA n=42 Participants Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate \[GA\]	Teriflunomide 14 mg + GA n=40 Participants Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate \[GA\]
Cerebral MRI Assessment: Total Volume of Gd-enhancing T1-lesions Per Scan	0.068 mililiters per scan	0.019 mililiters per scan	0.020 mililiters per scan	0.052 mililiters per scan	0.031 mililiters per scan	0.014 mililiters per scan

Adverse Events

Placebo + IFN-β

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Teriflunomide 7 mg + IFN-β

Serious events: 4 serious events

Other events: 33 other events

Deaths: 0 deaths

Teriflunomide 14 mg + IFN-β

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Placebo + GA

Serious events: 6 serious events

Other events: 34 other events

Deaths: 0 deaths

Teriflunomide 7 mg + GA

Serious events: 5 serious events

Other events: 30 other events

Deaths: 0 deaths

Teriflunomide 14 mg + GA

Serious events: 2 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo + IFN-β n=41 participants at risk Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 participants at risk Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 participants at risk Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=40 participants at risk Placebo (for Teriflunomide) once daily concomitantly with glatiramer acetate \[GA\]	Teriflunomide 7 mg + GA n=42 participants at risk Teriflunomide 7 mg once daily concomitantly with glatiramer acetate \[GA\]	Teriflunomide 14 mg + GA n=41 participants at risk Teriflunomide 14 mg once daily concomitantly with glatiramer acetate \[GA\]
Nervous system disorders Muscle spasticity	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Ear and labyrinth disorders Vertigo	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Abscess	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Cystitis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Herpes zoster	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Lobar pneumonia	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Mastoiditis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Otitis media	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Psychiatric disorders Suicidal ideation	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Psychiatric disorders Suicide attempt	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Cerebral ischaemia	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Epilepsy	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Vascular disorders Deep vein thrombosis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Vascular disorders Hypertension	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Hepatobiliary disorders Cholecystitis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Musculoskeletal and connective tissue disorders Pseudarthrosis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Alanine aminotransferase increased	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.8% 2/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Hepatic enzyme increased	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Injury, poisoning and procedural complications Ankle fracture	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Injury, poisoning and procedural complications Fall	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).

Other adverse events

Measure	Placebo + IFN-β n=41 participants at risk Placebo (for teriflunomide) once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 7 mg + IFN-β n=37 participants at risk Teriflunomide 7 mg once daily concomitantly with interferon-β \[IFN-β\]	Teriflunomide 14 mg + IFN-β n=38 participants at risk Teriflunomide 14 mg once daily concomitantly with interferon-β \[IFN-β\]	Placebo + GA n=40 participants at risk Placebo (for Teriflunomide) once daily concomitantly with glatiramer acetate \[GA\]	Teriflunomide 7 mg + GA n=42 participants at risk Teriflunomide 7 mg once daily concomitantly with glatiramer acetate \[GA\]	Teriflunomide 14 mg + GA n=41 participants at risk Teriflunomide 14 mg once daily concomitantly with glatiramer acetate \[GA\]
Skin and subcutaneous tissue disorders Dry skin	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Skin and subcutaneous tissue disorders Rash	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	14.6% 6/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Musculoskeletal and connective tissue disorders Back pain	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.5% 4/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Musculoskeletal and connective tissue disorders Pain in extremity	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.0% 4/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Renal and urinary disorders Micturition urgency	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
General disorders Asthenia	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.9% 3/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
General disorders Fatigue	9.8% 4/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	13.2% 5/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	17.5% 7/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	9.5% 4/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	17.1% 7/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
General disorders Oedema peripheral	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.5% 3/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.8% 2/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Alanine aminotransferase increased	14.6% 6/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	18.9% 7/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	31.6% 12/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Aspartate aminotransferase increased	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	18.9% 7/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.5% 4/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Bronchitis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Ear infection	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Gastroenteritis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.5% 3/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Influenza	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Nasopharyngitis	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	8.1% 3/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	13.2% 5/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	15.0% 6/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	16.7% 7/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	9.8% 4/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Respiratory tract infection	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Respiratory tract infection viral	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	12.5% 5/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.8% 2/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Sinusitis	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	9.8% 4/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Upper respiratory tract infection	9.8% 4/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	15.0% 6/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.8% 2/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	9.8% 4/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Infections and infestations Urinary tract infection	17.1% 7/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.8% 4/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	15.0% 6/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	11.9% 5/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	9.8% 4/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Psychiatric disorders Anxiety	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Psychiatric disorders Depression	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	11.9% 5/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Psychiatric disorders Insomnia	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.9% 3/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Carpal tunnel syndrome	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Dizziness	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.5% 3/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Headache	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	15.8% 6/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	17.5% 7/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	14.3% 6/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	17.1% 7/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Hypoaesthesia	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.8% 2/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Muscle spasticity	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	9.5% 4/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Paraesthesia	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Nervous system disorders Sciatica	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Ear and labyrinth disorders Vertigo	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.5% 3/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Vascular disorders Hypertension	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	8.1% 3/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.5% 4/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Respiratory, thoracic and mediastinal disorders Cough	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.4% 2/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Gastrointestinal disorders Abdominal discomfort	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Gastrointestinal disorders Abdominal pain upper	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.9% 3/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Gastrointestinal disorders Constipation	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.8% 2/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	9.8% 4/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Gastrointestinal disorders Diarrhoea	14.6% 6/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.8% 4/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.5% 4/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.0% 2/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.1% 3/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	19.5% 8/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Gastrointestinal disorders Nausea	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	13.2% 5/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.5% 3/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	11.9% 5/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	12.2% 5/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Gastrointestinal disorders Vomiting	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.5% 4/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Skin and subcutaneous tissue disorders Alopecia	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	8.1% 3/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.9% 3/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	11.9% 5/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	17.1% 7/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Blood creatine phosphokinase increased	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	8.1% 3/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.6% 1/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Blood pressure increased	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.9% 3/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Blood triglycerides increased	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Lipase increased	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Lymphocyte count decreased	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.8% 4/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	13.2% 5/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Neutrophil count decreased	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.5% 4/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations Protein urine present	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Investigations White blood cell count decreased	7.3% 3/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	8.1% 3/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	10.5% 4/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Injury, poisoning and procedural complications Contusion	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.7% 1/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.5% 1/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	4.9% 2/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
Injury, poisoning and procedural complications Procedural pain	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/37 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	5.3% 2/38 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/40 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	2.4% 1/42 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).	0.00% 0/41 • All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit. The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).

Additional Information

Trial Transparency Team

sanofi-aventis

Email: Contact_US@sanofi-aventis.com

Results disclosure agreements

• Principal investigator is a sponsor employee If no publication has occurred within 12 months after trial completion, the Investigator can publish the results. Prior to publication, the sponsor shall review the manuscript and can request changes, provided they do not jeopardize the accuracy and/or the scientific value of the publication. The approval is given in writing by the sponsor, not exceeding 90 days. To protect by property right the sponsor can postpone the publication of any information, for a period not exceeding 18 months.
• Publication restrictions are in place

Restriction type: OTHER