Trial Outcomes & Findings for A Tolerability Study of ALKS 8700 in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) EVOLVE-MS-2 (NCT NCT03093324)

Last Updated: 2020-07-14

Results Overview

IGISIS assessed the intensity of five individual GI symptoms: nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea. Participants rated the intensity of each individual symptom via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). IGISIS was completed by the participants using e-diaries.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

506 participants

Primary outcome timeframe

End of treatment (up to Week 6) for both Parts A and B

Results posted on

2020-07-14

Participant Flow

Participants were enrolled at 70 investigative sites in the United States (US), Germany, and Poland from March 15, 2017 to June 27, 2019.

A total of 506 participants with relapsing remitting multiple-sclerosis were enrolled in this study. Of which 504 participants received study drug and randomized in Parts A and B of the study (253 participants in ALKS 8700 group and 251 in Dimethyl Fumarate group). A total of 478 participants completed the study.

Participant milestones

Participant milestones
Measure	ALKS 8700 Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Overall Study STARTED	254	252
Overall Study Safety Population	253	251
Overall Study COMPLETED	245	233
Overall Study NOT COMPLETED	9	19

Reasons for withdrawal

Reasons for withdrawal
Measure	ALKS 8700 Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Overall Study Adverse Event	4	15
Overall Study Lost to Follow-up	1	0
Overall Study Protocol Deviation	2	2
Overall Study Withdrawal by Subject	2	2

Baseline Characteristics

A Tolerability Study of ALKS 8700 in Subjects With Relapsing Remitting Multiple Sclerosis (RRMS) EVOLVE-MS-2

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=251 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.	Total n=504 Participants Total of all reporting groups
Age, Continuous	43.7 years STANDARD_DEVIATION 10.96 • n=39 Participants	43.7 years STANDARD_DEVIATION 9.90 • n=41 Participants	43.7 years STANDARD_DEVIATION 10.44 • n=35 Participants
Sex: Female, Male Female	177 Participants n=39 Participants	190 Participants n=41 Participants	367 Participants n=35 Participants
Sex: Female, Male Male	76 Participants n=39 Participants	61 Participants n=41 Participants	137 Participants n=35 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	248 Participants n=39 Participants	241 Participants n=41 Participants	489 Participants n=35 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 Participants n=39 Participants	10 Participants n=41 Participants	15 Participants n=35 Participants
Race/Ethnicity, Customized White	232 Participants n=39 Participants	227 Participants n=41 Participants	459 Participants n=35 Participants
Race/Ethnicity, Customized Black or African American	20 Participants n=39 Participants	20 Participants n=41 Participants	40 Participants n=35 Participants
Race/Ethnicity, Customized Other	0 Participants n=39 Participants	2 Participants n=41 Participants	2 Participants n=35 Participants
Race/Ethnicity, Customized Asian	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Race/Ethnicity, Customized Multiple races	1 Participants n=39 Participants	0 Participants n=41 Participants	1 Participants n=35 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants

PRIMARY outcome

Timeframe: End of treatment (up to Week 6) for both Parts A and B

Population: The full analysis set (FAS) population included all enrolled participants in the Safety population who had at least one postbaseline GI tolerability assessment (such as IGISIS) on or before the last dose date.

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Days With Any Individual Gastrointestinal Symptom and Impact Scale (IGISIS) Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B	1.5 days Standard Deviation 2.85	2.5 days Standard Deviation 4.68

SECONDARY outcome

Timeframe: End of treatment (up to Week 6) for Part B

Population: The FAS population included all enrolled participants in the Safety population who had at least one postbaseline GI tolerability assessment (such as IGISIS) on or before the last dose date. Number analyzed are the participants who were evaluated for this outcome measure.

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Days With Any IGISIS Individual Symptom Intensity Score ≥2 Relative to Exposure Days in Part B	1.3 days Standard Deviation 2.70	2.2 days Standard Deviation 4.22

SECONDARY outcome

Timeframe: End of treatment (up to Week 6) for both Parts A and B

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Days With Any IGISIS Individual Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B	2.9 days Standard Deviation 4.46	3.9 days Standard Deviation 5.84

SECONDARY outcome

Timeframe: End of treatment (up to Week 6) for both Parts A and B

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Days With Any IGISIS Individual Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B	0.9 days Standard Deviation 2.25	1.5 days Standard Deviation 3.85

SECONDARY outcome

Timeframe: End of treatment (up to Week 6) for both Parts A and B

Population: The FAS population included all enrolled participants in the Safety population who had at least one postbaseline GI tolerability assessment (such as GGISIS) on or before the last dose date. Number analyzed are the participants who were evaluated for this outcome measure.

GGISIS is a global scale to assess the overall intensity of GI symptoms (nausea, vomiting, upper abdominal pain, lower abdominal pain, and diarrhea). Participants rated the intensity of GI symptoms via an 11-point numeric rating scale ranging from 0 (did not have) to 10 (extreme). GGISIS was completed by the participants using e-diaries.

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Days With a Global GI Symptom and Impact Scale (GGISIS) Symptom Intensity Score ≥1 Relative to Exposure Days in Parts A and B	2.1 days Standard Deviation 4.43	2.8 days Standard Deviation 5.19

SECONDARY outcome

Timeframe: End of treatment (up to Week 6) for both Parts A and B

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Days With a GGISIS Symptom Intensity Score ≥2 Relative to Exposure Days in Parts A and B	1.1 days Standard Deviation 3.25	1.5 days Standard Deviation 3.53

SECONDARY outcome

Timeframe: End of treatment (up to Week 6) for both Parts A and B

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Days With a GGISIS Symptom Intensity Score ≥3 Relative to Exposure Days in Parts A and B	0.7 days Standard Deviation 2.26	0.9 days Standard Deviation 2.57

SECONDARY outcome

Timeframe: End of treatment (up to Week 6) for both Parts A and B

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=249 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B Nausea	0.9 score on a scale Standard Deviation 1.55	1.2 score on a scale Standard Deviation 1.98
Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B Vomiting	0.2 score on a scale Standard Deviation 0.74	0.6 score on a scale Standard Deviation 1.84
Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B Upper Abdominal Pain	0.8 score on a scale Standard Deviation 1.58	1.3 score on a scale Standard Deviation 2.06
Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B Lower Abdominal Pain	0.8 score on a scale Standard Deviation 1.60	1.0 score on a scale Standard Deviation 1.84
Worst IGISIS Individual Symptom Intensity Score During the 5-Week Treatment Period in Parts A and B Diarrhea	1.1 score on a scale Standard Deviation 2.09	1.3 score on a scale Standard Deviation 2.19

SECONDARY outcome

Timeframe: End of study (up to Week 10)

Population: The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.

An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Outcome measures

Outcome measures
Measure	ALKS 8700 n=253 Participants Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=251 Participants Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Number of Participants With Adverse Events (AEs)	198 participants	210 participants

Adverse Events

ALKS 8700

Serious events: 4 serious events

Other events: 175 other events

Deaths: 0 deaths

Dimethyl Fumarate (DMF)

Serious events: 3 serious events

Other events: 191 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ALKS 8700 n=253 participants at risk Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=251 participants at risk Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Cardiac disorders Atrial fibrillation	0.40% 1/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	0.00% 0/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Hepatobiliary disorders Cholecystitis	0.00% 0/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	0.40% 1/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Nervous system disorders Multiple sclerosis relapse	1.2% 3/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	0.80% 2/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Psychiatric disorders Suicide attempt	0.40% 1/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	0.00% 0/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.

Other adverse events

Additional Information

Biogen Study Medical Director

Biogen

Phone: 866-633-4636

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	ALKS 8700 n=253 participants at risk Participants received ALKS 8700 231 milligrams (mg) along with ALKS 8700-matching placebo, oral capsules, twice daily (BID), for Week 1, followed by administration of ALKS 8700 462 mg, oral capsules, BID, for Week 2 to 5.	Dimethyl Fumarate (DMF) n=251 participants at risk Participants received DMF 120 mg along with DMF-matching placebo, oral capsules, BID for Week 1, followed by administration of DMF 240 mg and DMF-matching placebo, oral capsules, BID, for week 2 to 5.
Gastrointestinal disorders Abdominal pain	6.3% 16/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	9.6% 24/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Gastrointestinal disorders Abdominal pain lower	5.9% 15/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	6.8% 17/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Gastrointestinal disorders Abdominal pain upper	6.7% 17/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	15.5% 39/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Gastrointestinal disorders Diarrhoea	15.4% 39/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	22.3% 56/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Gastrointestinal disorders Nausea	14.6% 37/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	20.7% 52/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Gastrointestinal disorders Vomiting	3.6% 9/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	8.8% 22/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
General disorders Fatigue	2.4% 6/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	5.2% 13/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
General disorders Feeling hot	1.6% 4/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	2.4% 6/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Infections and infestations Nasopharyngitis	5.9% 15/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	4.4% 11/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Infections and infestations Upper respiratory tract infection	3.6% 9/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	3.6% 9/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Infections and infestations Urinary tract infection	3.2% 8/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	3.6% 9/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Investigations Alanine aminotransferase increased	5.5% 14/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	3.6% 9/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Investigations Aspartate aminotransferase increased	3.6% 9/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	2.0% 5/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Investigations Urine albumin/creatinine ratio increased	2.4% 6/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	0.80% 2/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Nervous system disorders Headache	4.0% 10/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	5.6% 14/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Nervous system disorders Multiple sclerosis relapse	3.2% 8/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	2.0% 5/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Skin and subcutaneous tissue disorders Erythema	7.9% 20/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	8.4% 21/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Skin and subcutaneous tissue disorders Generalised erythema	1.6% 4/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	3.6% 9/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Skin and subcutaneous tissue disorders Pruritus	7.1% 18/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	7.2% 18/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Skin and subcutaneous tissue disorders Pruritus generalised	0.79% 2/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	2.4% 6/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Skin and subcutaneous tissue disorders Rash	1.6% 4/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	2.4% 6/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.
Vascular disorders Flushing	32.8% 83/253 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.	40.6% 102/251 • End of study (up to Week 10) The Safety population included all enrolled participants who had received at least one dose of study drug during the double-blind Treatment Period.