Trial Outcomes & Findings for THOR Study: A Study of Continued Herceptin (Trastuzumab) in Combination With Second Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer. (NCT NCT00448279)

NCT ID: NCT00448279

Last Updated: 2014-10-24

Results Overview

PFS was defined as the time from randomization to the date of documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or the date of occurrence of a second primary cancer, or date of death from any cause, whichever comes first. Participants were censored at the last tumour evaluation.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 58 participants
• Primary outcome timeframe: Baseline (BL) and every 8 weeks thereafter
• Results posted on: 2014-10-24

Participant Flow

Participant milestones

Measure	Chemotherapy Alone Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy Plus (+) Trastuzumab Participants received trastuzumab at either 2 milligrams per kilogram (mg/kg), intravenously (IV), every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Overall Study STARTED	29	29
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	29	29

Reasons for withdrawal

Measure	Chemotherapy Alone Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy Plus (+) Trastuzumab Participants received trastuzumab at either 2 milligrams per kilogram (mg/kg), intravenously (IV), every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Overall Study Lost to Follow-up	2	2
Overall Study Adverse Event	1	1
Overall Study Disease progression	16	18
Overall Study Withdrawal by Subject	4	3
Overall Study Other	6	4
Overall Study Protocol Violation	0	1

Baseline Characteristics

THOR Study: A Study of Continued Herceptin (Trastuzumab) in Combination With Second Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer.

Baseline characteristics by cohort

Measure	Chemotherapy Alone n=29 Participants Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=29 Participants Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.	Total n=58 Participants Total of all reporting groups
Age, Continuous	59 years n=93 Participants	57 years n=4 Participants	58 years n=27 Participants
Sex: Female, Male Female	29 Participants n=93 Participants	29 Participants n=4 Participants	58 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (BL) and every 8 weeks thereafter

Population: ITT population

PFS was defined as the time from randomization to the date of documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or the date of occurrence of a second primary cancer, or date of death from any cause, whichever comes first. Participants were censored at the last tumour evaluation.

Outcome measures

Measure	Chemotherapy Alone n=29 Participants Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=29 Participants Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Progression-Free Survival (PFS) - Percentage of Participants With an Event	58.6 percentage of participants	58.6 percentage of participants

PRIMARY outcome

Timeframe: BL and every 8 weeks thereafter

Population: ITT population

The median time from randomization to PFS event. Participants were censored at the last tumour evaluation.

Outcome measures

Measure	Chemotherapy Alone n=29 Participants Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=29 Participants Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Progression-Free Survival - Time to Event	9.7 months Interval 5.5 to 18.9	9.4 months Interval 6.7 to 12.0

SECONDARY outcome

Timeframe: BL and every 8 weeks thereafter

Population: ITT population

OS was defined as the time from randomization to the date of death from any cause. Participants were censored at the last contact date at which the participant was known to be alive.

Outcome measures

Measure	Chemotherapy Alone n=29 Participants Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=29 Participants Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Overall Survival (OS) - Percentage of Participants With an Event	55.2 percentage of participants	34.5 percentage of participants

SECONDARY outcome

Timeframe: BL and every 8 weeks thereafter

Population: ITT population

The median time from randomization to OS event. Participants were censored at the last contact date at which the participant was known to be alive.

Outcome measures

Measure	Chemotherapy Alone n=29 Participants Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=29 Participants Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Overall Survival - Time to Event	19.1 months Interval 17.0 to 32.7	26.7 months Interval 14.0 to Upper limit of the 95 percent (%) confidence interval (CI) could not be determined as follow-up was too short to observe enough survival events for complete data estimation.

SECONDARY outcome

Timeframe: BL and every 8 weeks thereafter

Population: ITT population

BOR was defined as the best objective response observed during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR): disappearance of all target lesions (TLs), with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters (mm). Partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. Progressive disease (PD): at least a 20% increase in the sum of diameters of TLs, taking as a reference the smallest sum on study (this included the BL sum if that is the smallest on study). In addition to the relative increase in 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Stable disease (SD) was defined as neither sufficient shrinkages to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Measure	Chemotherapy Alone n=29 Participants Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=29 Participants Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Percentage of Participants by Best Overall Response (BOR) CR	0 percentage of participants	10.3 percentage of participants
Percentage of Participants by Best Overall Response (BOR) SD	24.1 percentage of participants	24.1 percentage of participants
Percentage of Participants by Best Overall Response (BOR) PR	27.6 percentage of participants	20.7 percentage of participants
Percentage of Participants by Best Overall Response (BOR) PD	17.2 percentage of participants	13.8 percentage of participants
Percentage of Participants by Best Overall Response (BOR) Not Evaluated	31.0 percentage of participants	31.0 percentage of participants

SECONDARY outcome

Timeframe: BL and every 8 weeks thereafter

Population: ITT population

BOR was defined as the best objective response observed during the treatment period according to RECIST version 1.1. CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. PD: at least a 20% increase in the sum of diameters of TLs, taking as a reference the smallest sum on study (this included the BL sum if that is the smallest on study). In addition to the relative increase in 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. SD: neither sufficient shrinkages to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Measure	Chemotherapy Alone n=29 Participants Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=29 Participants Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Percentage of Participants With a Best Overall Response of CR or PR	27.6 percentage of participants Interval 12.7 to 47.2	31.0 percentage of participants Interval 15.3 to 50.8

Adverse Events

Chemotherapy Alone

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Chemotherapy + Trastuzumab

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Chemotherapy Alone n=26 participants at risk Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=28 participants at risk Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Blood and lymphatic system disorders Febrile neutropenia	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders General Malaise	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Gastric volvulus	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Renal and urinary disorders Acute renal failure	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Hospitalisation for intrapleuric chemotherapy and thoracentesis	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.

Other adverse events

Measure	Chemotherapy Alone n=26 participants at risk Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	Chemotherapy + Trastuzumab n=28 participants at risk Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.
Blood and lymphatic system disorders Leukopenia	50.0% 13/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	25.0% 7/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Blood and lymphatic system disorders Neutropenia	61.5% 16/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	32.1% 9/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Blood and lymphatic system disorders Febrile Neutropenia	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Nausea	30.8% 8/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Mucositis	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Blood and lymphatic system disorders Anemia	19.2% 5/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Skin and subcutaneous tissue disorders Alopecia	11.5% 3/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	10.7% 3/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Psychiatric disorders Depression	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Hepatobiliary disorders Liver-GOT,GPT	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Other - unspecified	30.8% 8/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	32.1% 9/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Nervous system disorders Neuro device	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	10.7% 3/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Psychiatric disorders Anxiety	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	7.1% 2/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Pain	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Diarrhea	7.7% 2/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	17.9% 5/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Nervous system disorders Dysgeusia	7.7% 2/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Skin and subcutaneous tissue disorders Cutanea SMP	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	10.7% 3/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Nervous system disorders Vertigo syndrome	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Scapular pain	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Metabolism and nutrition disorders Anorexia	7.7% 2/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Musculoskeletal and connective tissue disorders Dorsal spine pain	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Fever	19.2% 5/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	10.7% 3/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Vomiting	19.2% 5/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Hepatobiliary disorders Liver-ALP	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Musculoskeletal and connective tissue disorders Bone pain	7.7% 2/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	10.7% 3/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Asthenia	26.9% 7/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Musculoskeletal and connective tissue disorders Pain - Spine	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Psychiatric disorders Decline in mood	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.5% 3/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Metabolism and nutrition disorders Hypocalcemia	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Immune system disorders Allergy	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Vascular disorders Hypertension	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	7.1% 2/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Heartburn	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Nervous system disorders Headache	7.7% 2/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Musculoskeletal and connective tissue disorders Plantar foot pain	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Respiratory, thoracic and mediastinal disorders Exertional dyspnea	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Hand fissures	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Nervous system disorders Paresthesia - hand	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Gingival	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Musculoskeletal and connective tissue disorders Pelvic pain	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Nervous system disorders Memory deficit	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Respiratory, thoracic and mediastinal disorders Cough	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Abdominal cramps	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Epigastric pain	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Psychiatric disorders Insomnia	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Sore throat	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Edema	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Constipation	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Infections and infestations Urinary infection	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Musculoskeletal and connective tissue disorders Right upper limb pain	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Musculoskeletal and connective tissue disorders Cranial pain	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Nervous system disorders Paraesthesia hand and feet	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Achy hands and feet	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
General disorders Fatigue	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Investigations Hypercholesterolemia	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Cardiac disorders Pericardial effusion	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Gastrointestinal disorders Bilateral mandibular pain	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Skin and subcutaneous tissue disorders Erythema hand and foot	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Hepatobiliary disorders Liver-bilirubin	0.00% 0/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	3.6% 1/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.
Metabolism and nutrition disorders Diabetes	3.8% 1/26 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.	0.00% 0/28 • Adverse events (AEs) were recorded throughout the study. Drug-related serious AEs (SAEs) were collected, regardless of the time elapsed from last study treatment administration, even if the study had been closed. All randomized participants who received at least 1 dose of study treatment were included in the safety evaluation.

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER