Trial Outcomes & Findings for Phase IIa Vorinostat (MK0683, Suberoylanilide Hydroxamic Acid (SAHA)) Study in Lower Risk Myelodysplastic Syndromes (0683-064) (NCT NCT00486720)

NCT ID: NCT00486720

Last Updated: 2015-07-03

Results Overview

Number of responders is defined as the number of patients in the analysis population who have complete response (CR), partial response (PR), or hematologic improvement (HI) per International Working Group Response Criteria during the course of the study. Confirmation of CR or PR will require a second assessment performed 4 weeks or more after the initial assessment. Confirmation of HI will require a second assessment performed 8 weeks or more after the initial assessment. Number of non-responders is defined as the number of patients who did not achieve CR, PR or HI in the study.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: 2 Years
• Results posted on: 2015-07-03

Participant Flow

Date of first patient in was 26-Jun-2007. The date of last patient last visit for the study was 16-Jul-2009.

Vorinostat was studied in patients who were first stratified by their International Prognostic Scoring System for myelodysplastic syndrome (low versus intermediate-1) and than randomized into one of two dose schedules.

Participant milestones

Measure	Vorinostat Once Daily Dose Schedule Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle.	Vorinostat Thrice Daily Dose Schedule Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle.
Overall Study STARTED	10	12
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	10	12

Reasons for withdrawal

Measure	Vorinostat Once Daily Dose Schedule Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle.	Vorinostat Thrice Daily Dose Schedule Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle.
Overall Study Adverse Event	1	2
Overall Study Lack of Efficacy	4	6
Overall Study Physician Decision	1	2
Overall Study Protocol Violation	1	0
Overall Study Withdrawal by Subject	3	1
Overall Study Progressive Disease	0	1

Baseline Characteristics

Phase IIa Vorinostat (MK0683, Suberoylanilide Hydroxamic Acid (SAHA)) Study in Lower Risk Myelodysplastic Syndromes (0683-064)

Baseline characteristics by cohort

Measure	Vorinostat Once Daily Dose Schedule n=9 Participants Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle.	Vorinostat Thrice Daily Dose Schedule n=12 Participants Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle.	Total n=21 Participants Total of all reporting groups
Age, Continuous	69.0 years STANDARD_DEVIATION 18.5 • n=5 Participants	64.0 years STANDARD_DEVIATION 10.5 • n=7 Participants	66.0 years STANDARD_DEVIATION 14.1 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Race/Ethnicity, Customized Black	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Scale Status 0 = Normal Activity	4 participants n=5 Participants	10 participants n=7 Participants	14 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Scale Status 1 = Symptoms, but ambulatory	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Scale Status 2 = In bed < 50% of the time	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
International Prognostic Scoring System Risk (IPSS) Low	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
International Prognostic Scoring System Risk (IPSS) Intermediate-1	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Prior Myelodysplastic Syndromes Therapy Yes	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Prior Myelodysplastic Syndromes Therapy No	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Full analysis set (FAS) population is the analysis population. This population consists of all randomized patients who have received at least one dose of study medication.

Number of responders is defined as the number of patients in the analysis population who have complete response (CR), partial response (PR), or hematologic improvement (HI) per International Working Group Response Criteria during the course of the study. Confirmation of CR or PR will require a second assessment performed 4 weeks or more after the initial assessment. Confirmation of HI will require a second assessment performed 8 weeks or more after the initial assessment. Number of non-responders is defined as the number of patients who did not achieve CR, PR or HI in the study.

Outcome measures

Measure	Vorinostat Once Daily Dose Schedule n=9 Participants Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle.	Vorinostat Thrice Daily Dose Schedule n=12 Participants Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle.
Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria Non-responder	9 Participants	12 Participants
Number of Responders and Number of Non-responders Defined by International Working Group Response Criteria Responder	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Every 21 days while on therapy and at 30 days after the last dose of study therapy

Outcome measures

Measure	Vorinostat Once Daily Dose Schedule n=9 Participants Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle.	Vorinostat Thrice Daily Dose Schedule n=12 Participants Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle.
Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. With one or more adverse events	9 Participants	12 Participants
Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. With serious drug-related adverse events	0 Participants	2 Participants
Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. With no adverse events	0 Participants	0 Participants
Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. With drug-related adverse events	4 Participants	11 Participants
Safety and Tolerability as Assessed by the Number of Participants With Adverse Events. With serious adverse events	2 Participants	5 Participants

Adverse Events

Vorinostat Once Daily Dose Schedule

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Vorinostat Thrice Daily Dose Schedule

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Vorinostat Once Daily Dose Schedule n=9 participants at risk Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle.	Vorinostat Thrice Daily Dose Schedule n=12 participants at risk Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle.
Blood and lymphatic system disorders Anaemia	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Blood and lymphatic system disorders Neutropenia	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Blood and lymphatic system disorders Splenic haemorrhage	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Cardiac disorders Pericardial effusion	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
General disorders Disease progression	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Eye infection	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Lung infection	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Pharyngitis	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Pneumonia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Urinary tract infection	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Nervous system disorders Neuropathy peripheral	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Psychiatric disorders Confusional state	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Renal and urinary disorders Urinary retention	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.

Other adverse events

Measure	Vorinostat Once Daily Dose Schedule n=9 participants at risk Vorinostat 400 mg once daily for 14 consecutive days in a 21 day cycle.	Vorinostat Thrice Daily Dose Schedule n=12 participants at risk Vorinostat 200 mg three times daily for 14 consecutive days in a 21 day cycle.
Blood and lymphatic system disorders Anaemia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	58.3% 7/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Blood and lymphatic system disorders Leukopenia	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Blood and lymphatic system disorders Neutropenia	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	33.3% 4/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Cardiac disorders Left ventricular dysfunction	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Cardiac disorders Left ventricular hypertrophy	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Cardiac disorders Palpitations	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Cardiac disorders Supraventricular tachycardia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Ear and labyrinth disorders Ear pain	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Eye disorders Eye irritation	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Eye disorders Eye pruritus	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Abdominal pain	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Abdominal pain upper	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Constipation	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Diarrhoea	55.6% 5/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	91.7% 11/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Dry mouth	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Dyspepsia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Eructation	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Flatulence	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Haemorrhoids	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Nausea	55.6% 5/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	75.0% 9/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Oesophagitis	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Retching	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Stomatitis	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Tongue discolouration	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Gastrointestinal disorders Vomiting	44.4% 4/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	41.7% 5/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
General disorders Chest pain	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
General disorders Chills	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
General disorders Fatigue	44.4% 4/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	58.3% 7/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
General disorders Pain	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
General disorders Pyrexia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Hepatobiliary disorders Hyperbilirubinaemia	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Cellulitis	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Cystitis	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Hordeolum	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Paronychia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Pneumonia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Rhinitis	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Infections and infestations Skin bacterial infection	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Investigations Alanine aminotransferase increased	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Investigations Aspartate aminotransferase increased	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Investigations Blood alkaline phosphatase increased	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Investigations Blood creatinine increased	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Investigations Haematocrit decreased	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Investigations Red blood cell count decreased	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Anorexia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	41.7% 5/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Dehydration	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Hyperglycaemia	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Hyperuricaemia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	33.3% 4/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Hypomagnesaemia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Metabolism and nutrition disorders Increased appetite	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Musculoskeletal and connective tissue disorders Arthritis	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Musculoskeletal and connective tissue disorders Back pain	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Musculoskeletal and connective tissue disorders Groin pain	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Musculoskeletal and connective tissue disorders Joint swelling	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Musculoskeletal and connective tissue disorders Muscle spasms	33.3% 3/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Musculoskeletal and connective tissue disorders Muscular weakness	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Nervous system disorders Balance disorder	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Nervous system disorders Cognitive disorder	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Nervous system disorders Dizziness	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	25.0% 3/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Nervous system disorders Dysgeusia	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Nervous system disorders Somnolence	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Nervous system disorders Syncope	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Epistaxis	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Skin and subcutaneous tissue disorders Pruritus	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Respiratory, thoracic and mediastinal disorders Rash	22.2% 2/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	16.7% 2/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Skin and subcutaneous tissue disorders Skin lesion	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Vascular disorders Flushing	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Vascular disorders Hot flush	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Vascular disorders Hypotension	0.00% 0/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	8.3% 1/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.
Vascular disorders Orthostatic hypotension	11.1% 1/9 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.	0.00% 0/12 • Serious and non-serious adverse experiences occurring from the time of consent up through 30 days after the last dose of study drug were reported. One patient was randomized to the Once Daily Dose Schedule, but discontinued before receiving study medication due to a protocol violation and is not included in the safety assessment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

• Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER