Trial Outcomes & Findings for A Crossover Study to Assess the Effects of Vorinostat (MK0683, SAHA) in Patients With Advanced Cancer (0683-070)(COMPLETED) (NCT NCT00632931)

Last Updated: 2015-07-30

Results Overview

The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

25 participants

Primary outcome timeframe

Baseline and 0.5 hours

Results posted on

2015-07-30

Participant Flow

Eric Rubin, M.D., The Cancer Institute of New Jersey, New Brunswick, New Jersey; Pamela Munster, M.D., H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Prof. Dr. Simon van Belle, University Hospital of Ghent, Ghent, Belgium. Dosing initiated on 16-Jul-2007 and completed on 05-Feb-2009.

Enrolled patients were assigned to 1 of 2 dose sequences (vorinostat then placebo or placebo then vorinostat) in Part 1 of the study to determine the effect of vorinostat on the QTcF (Fridericia-corrected QT) interval. Following Part 1, active patients continued into Part 2, daily dosing of vorinostat.

Participant milestones

Participant milestones
Measure	Vorinostat Then Placebo: Part 1 Single dose 800 mg vorinostat in Period 1 followed by a three day wash out period, then matching placebo in Period 2. Following the last dose of study drug, there was a minimum 5 day washout before entering Part 2.	Placebo Then Vorinostat: Part 1 Single dose matching placebo in Period 1 followed by a three day wash out period, then single dose 800 mg vorinostat in Period 2. Following the last dose of study drug, there was a minimum 5 day washout before entering Part 2.	All Participants: Part 2 Vorinostat 400 mg once daily. Ten participants changed dosage to vorinostat 300 mg daily during Part 2.
Part 1, Period 1 STARTED	13	12	0
Part 1, Period 1 COMPLETED	11	12	0
Part 1, Period 1 NOT COMPLETED	2	0	0
Part 1, Washout STARTED	11	12	0
Part 1, Washout COMPLETED	11	12	0
Part 1, Washout NOT COMPLETED	0	0	0
Part 1, Period 2 STARTED	11	12	0
Part 1, Period 2 COMPLETED	11	12	0
Part 1, Period 2 NOT COMPLETED	0	0	0
Post-Part 1 Washout STARTED	12	12	0
Post-Part 1 Washout COMPLETED	12	12	0
Post-Part 1 Washout NOT COMPLETED	0	0	0
Part 2 STARTED	0	0	24
Part 2 COMPLETED	0	0	0
Part 2 NOT COMPLETED	0	0	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Vorinostat Then Placebo: Part 1 Single dose 800 mg vorinostat in Period 1 followed by a three day wash out period, then matching placebo in Period 2. Following the last dose of study drug, there was a minimum 5 day washout before entering Part 2.	All Participants: Part 2 Vorinostat 400 mg once daily. Ten participants changed dosage to vorinostat 300 mg daily during Part 2.
Part 1, Period 1 Protocol Violation	1	0
Part 1, Period 1 Withdrawal by Subject	1	0
Part 2 Adverse Event	0	3
Part 2 Death	0	1
Part 2 Lack of Efficacy	0	17
Part 2 Withdrawal by Subject	0	3

Baseline Characteristics

A Crossover Study to Assess the Effects of Vorinostat (MK0683, SAHA) in Patients With Advanced Cancer (0683-070)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=25 Participants All Participants group includes data from all participants throughout Part 1 and Part 2 of the study.
Age, Continuous	59.4 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized Black	2 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants
Race/Ethnicity, Customized White	21 participants n=5 Participants
Cancer Type Ovarian	5 Participants n=5 Participants
Cancer Type Colon	3 Participants n=5 Participants
Cancer Type Lung	3 Participants n=5 Participants
Cancer Type Mesothelioma	3 Participants n=5 Participants
Cancer Type Uterine	2 Participants n=5 Participants
Cancer Type Soft Tissue	2 Participants n=5 Participants
Cancer Type Anal	1 Participants n=5 Participants
Cancer Type Basocellular	1 Participants n=5 Participants
Cancer Type Breast	1 Participants n=5 Participants
Cancer Type Gastrointestinal	1 Participants n=5 Participants
Cancer Type Mucinous carcinoma	1 Participants n=5 Participants
Cancer Type Pancreatic	1 Participants n=5 Participants
Cancer Type Thyroid	1 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Normal Activity	9 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Symptoms, but ambulatory	13 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = In bed <50% of the time	3 Participants n=5 Participants
Number of Prior Radiation Therapies None	14 Participants n=5 Participants
Number of Prior Radiation Therapies One Prior Radiation Therapy	7 Participants n=5 Participants
Number of Prior Radiation Therapies Two Prior Radiation Therapies	1 Participants n=5 Participants
Number of Prior Radiation Therapies Three or More Prior Radiation Therapies	3 Participants n=5 Participants
Number of Prior Systemic Anti-Cancer Therapies One Prior Systemic Anti-Cancer Therapy	0 Participants n=5 Participants
Number of Prior Systemic Anti-Cancer Therapies Two Prior Systemic Anti-Cancer Therapies	3 Participants n=5 Participants
Number of Prior Systemic Anti-Cancer Therapies Three or more Prior Systemic Anti-Cancer Therapies	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 0.5 hours

Population: All patients as treated population in Part 1 of the Study; 22 patients had QTcF data from the vorinostat period (One patient with protocol violation, and two patients without predose measurements were excluded) and 23 patients had QTcF data from the placebo period (one patient with protocol violation and one patient who discontinued were excluded)

Outcome measures

Outcome measures
Measure	Vorinostat n=23 Participants	Placebo n=22 Participants
Change From Baseline in QTcF at 0.5 Hours	1.78 milliseconds Interval -1.53 to 5.09	-1.22 milliseconds Interval -4.53 to 2.08

PRIMARY outcome

Timeframe: Baseline and 1 hour

Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The change from baseline in QTcF was calculated by subtracting the QTcF value at each timepoint from the QTcF baseline (predose) value.

Outcome measures

Outcome measures
Measure	Vorinostat n=23 Participants	Placebo n=22 Participants
Change From Baseline in QTcF at 1 Hour	0.22 milliseconds Interval -3.09 to 3.52	-1.23 milliseconds Interval -4.54 to 2.08

PRIMARY outcome

Timeframe: Baseline and 2 hours

Outcome measures

Outcome measures
Measure	Vorinostat n=23 Participants	Placebo n=23 Participants
Change From Baseline in QTcF at 2 Hours	1.09 milliseconds Interval -2.22 to 4.4	-1.98 milliseconds Interval -5.23 to 1.28

PRIMARY outcome

Timeframe: Baseline and 3 hours

Outcome measures

Outcome measures
Measure	Vorinostat n=23 Participants	Placebo n=23 Participants
Change From Baseline in QTcF at 3 Hours	1.32 milliseconds Interval -1.99 to 4.63	-1.52 milliseconds Interval -4.77 to 1.73

PRIMARY outcome

Timeframe: Baseline and 4 hours

The Fridericia correction of the QT interval (QTcF) was determined at each time point from five replicate measurements. The placebo-corrected change from baseline in QTcF was calculated by subtracting the QTcF change from baseline for placebo at each timepoint from the QTcF change from baseline for vorinostat at each timepoint.

Outcome measures

Outcome measures
Measure	Vorinostat n=23 Participants	Placebo n=23 Participants
Change From Baseline in QTcF at 4 Hours	4.95 milliseconds Interval 1.64 to 8.26	-1.49 milliseconds Interval -4.75 to 1.76

PRIMARY outcome

Timeframe: Baseline and 8 hours

Outcome measures

Outcome measures
Measure	Vorinostat n=23 Participants	Placebo n=22 Participants
Change From Baseline in QTcF at 8 Hours	-3.56 milliseconds Interval -6.87 to -0.25	-7.89 milliseconds Interval -11.2 to -4.58

PRIMARY outcome

Timeframe: Baseline and 12 hours

Outcome measures

Outcome measures
Measure	Vorinostat n=21 Participants	Placebo n=22 Participants
Change From Baseline in QTcF at 12 Hours	1.35 milliseconds Interval -2.08 to 4.78	-1.31 milliseconds Interval -4.62 to 2.0

PRIMARY outcome

Timeframe: Baseline and 24 hours

Outcome measures

Outcome measures
Measure	Vorinostat n=22 Participants	Placebo n=22 Participants
Change From Baseline in QTcF at 24 Hours	1.53 milliseconds Interval -1.84 to 4.98	-4.89 milliseconds Interval -8.29 to -1.67

Adverse Events

All Participants

Serious events: 11 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=25 participants at risk All Participants group includes data from all participants throughout Part 1 and Part 2 of the study.
Blood and lymphatic system disorders Anemia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Pain	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Ascites	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Constipation	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Diarrhea	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Small Intestinal Obstruction	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Vomiting	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Disease Progression	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Fatigue	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Pyrexia	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Hepatobiliary disorders Portal Vein Thrombosis	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Infections and infestations Cellulitis	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Infections and infestations Urinary Tract Infection	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Vascular disorders Peripheral Embolism	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.

Other adverse events

Other adverse events
Measure	All Participants n=25 participants at risk All Participants group includes data from all participants throughout Part 1 and Part 2 of the study.
Blood and lymphatic system disorders Anemia	16.0% 4/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Blood and lymphatic system disorders Leukocytosis	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Blood and lymphatic system disorders Leukopenia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Blood and lymphatic system disorders Lymphopenia	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Blood and lymphatic system disorders Thrombocytopenia	28.0% 7/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Eye disorders Dry Eye	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Cramp	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Discomfort	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Distension	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Fullness	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Pain	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Pain Lower	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Abdominal Pain Upper	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Constipation	48.0% 12/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Diarrhea	36.0% 9/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Dry Mouth	24.0% 6/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Dysphagia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Flatulence	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Gas	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Gas Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Gingival Bleeding	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Loose Stools	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Nausea	80.0% 20/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Gastrointestinal disorders Vomiting	40.0% 10/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Axillary Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Chest Pain	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Chills	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Early Satiety	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Fatigue	68.0% 17/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Fever	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Foot Edema	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Gait Unsteady	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Intermittent Pyrexia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Leg Edema	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Edema Lower Limb	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Suprapubic Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Weakness	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
General disorders Weakness Generalized	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Infections and infestations Candidiasis	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Infections and infestations Sinus Infection	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Infections and infestations Upper Respiratory Tract Infection	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Infections and infestations Urinary Tract Infection	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Infections and infestations Wound Infection	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Injury, poisoning and procedural complications Fall	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Alkaline Phosphatase Increased	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Bilirubin Increased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Carbon Dioxide Increased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Creatine Increased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Creatinine Increased	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Glucose Increased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Magnesium Decreased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Magnesium Increased	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Blood Potassium Decreased	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Electrocardiogram QT Corrected Interval Prolonged	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations International Normalized Ratio Increased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Neutrophil Count Increased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Prothrombin Time Prolonged	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Skin Turgor Decreased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations Weight Decreased	16.0% 4/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Investigations White Blood Cell Count Decreased	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Anorexia	64.0% 16/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Decreased Appetite	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Dehydration	16.0% 4/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Hyperchloremia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Hypercreatininemia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Hyperglycemia	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Hyperphosphatasemia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Metabolism and nutrition disorders Hypokalemia	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Musculoskeletal and connective tissue disorders Bone Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Musculoskeletal and connective tissue disorders Foot Cramps	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Musculoskeletal and connective tissue disorders Low Back Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Musculoskeletal and connective tissue disorders Pain In Hip	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Musculoskeletal and connective tissue disorders Pain In Leg	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Musculoskeletal and connective tissue disorders Shoulder Pain	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Musculoskeletal and connective tissue disorders Unilateral Leg Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Dizziness	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Dysphasia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Headache	12.0% 3/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Migraine	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Neuropathic Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Neuropathy	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Neuropathy Peripheral	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Numbness	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Numbness In Toes	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Paraesthesia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Taste Changed	24.0% 6/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Tingling	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Nervous system disorders Tingling Feet/Hands	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Psychiatric disorders Depression	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Psychiatric disorders Insomnia	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Psychiatric disorders Restlessness	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Renal and urinary disorders Bladder Discomfort	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Renal and urinary disorders Hematuria	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Renal and urinary disorders Nocturia	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Renal and urinary disorders Renal Insufficiency	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Renal and urinary disorders Urinary Incontinence	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Renal and urinary disorders Urine Discoloration	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Reproductive system and breast disorders Benign Prostatic Hypertrophy	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Reproductive system and breast disorders Breast Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Reproductive system and breast disorders Pelvic Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Reproductive system and breast disorders Spotting Vaginal	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Reproductive system and breast disorders Vaginal Pain	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Cough	32.0% 8/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Dry Cough	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	20.0% 5/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Dyspnea Exertional	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Hiccups	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	8.0% 2/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Congestion	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Sinus Congestion	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Respiratory, thoracic and mediastinal disorders Throat Irritation	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Skin and subcutaneous tissue disorders Dry Skin	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Skin and subcutaneous tissue disorders Skin Irritation	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Vascular disorders Flushing	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Vascular disorders Hypertension	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Vascular disorders Hypotension	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.
Vascular disorders Inferior Venacaval Thrombosis	4.0% 1/25 • Reported adverse experiences are those from the time patients began study treatment until the patient discontinued. The average AE reporting timeframe is 78 days.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

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