Trial Outcomes & Findings for Enzalutamide/Leuprolide +/- Abiraterone/Pred in Prostate (NCT NCT02268175)

Last Updated: 2022-04-19

Results Overview

pCR is defined as the absence of morphologically identifiable carcinoma in the radical prostatectomy (RP) specimen. MRD is defined as the largest cross-sectional dimension of residual tumor measuring \</= 0.5 cm. If the tumor is multifocal, the size of the largest focus will be used to determine the size of the residual tumor.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

75 participants

Primary outcome timeframe

after RP approximately 24 weeks from study entry

Results posted on

2022-04-19

Participant Flow

Participant milestones

Participant milestones
Measure	Enzalutamide + Abiraterone + Prednisone + Leuprolide Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	Enzalutamide + Leuprolide Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Overall Study STARTED	50	25
Overall Study COMPLETED	50	25
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Enzalutamide/Leuprolide +/- Abiraterone/Pred in Prostate

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ARM 1 n=50 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	Total n=75 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	63 years n=7 Participants	62 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants	25 Participants n=7 Participants	75 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	20 Participants n=7 Participants	65 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
National Comprehensive Cancer Network (NCCN) Risk Group High Risk	44 Participants n=5 Participants	21 Participants n=7 Participants	65 Participants n=5 Participants
National Comprehensive Cancer Network (NCCN) Risk Group Intermediate Risk	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: after RP approximately 24 weeks from study entry

Outcome measures

Outcome measures
Measure	ARM 1 n=50 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Percentage of Participants With Pathologic Complete Response (pCR) or Minimal Residual Disease (MRD)	30 percentage of participants Interval 18.0 to 45.0	16 percentage of participants Interval 5.0 to 36.0

SECONDARY outcome

Timeframe: after RP approximately 24 weeks from study entry

pCR is defined as the absence of morphologically identifiable carcinoma in the radical prostatectomy (RP) specimen.

Outcome measures

Outcome measures
Measure	ARM 1 n=50 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Participants With Pathologic Complete Response (pCR)	5 Participants	2 Participants

SECONDARY outcome

Timeframe: after RP approximately 24 weeks from study entry

RCB was analyzed using radical prostatectomy (RP) tissue. The largest area of tumor was measured by ruler and the longest tumor dimension in this area was used as the dimension for calculation.

Outcome measures

Outcome measures
Measure	ARM 1 n=50 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Residual Cancer Burden (RCB)	0.03 cm Interval 0.0 to 4.0	0.05 cm Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: after RP approximately 24 weeks from study entry

Participants were classified by presence or absence of positive surgical margins defined as margins, which are the edges of the removed tumor, that show some cancer cells.

Outcome measures

Outcome measures
Measure	ARM 1 n=50 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Positive Surgical Margin Status Absence	41 Participants	22 Participants
Positive Surgical Margin Status Presence	9 Participants	3 Participants

SECONDARY outcome

Timeframe: PSA was assessed at baseline and every cycle during neoadjuvant therapy (up to 24 weeks).

PSA nadir is the lowest PSA level recorded during neoadjuvant therapy.

Outcome measures

Outcome measures
Measure	ARM 1 n=50 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 Participants Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Median Prostate Specific Antigen (PSA) Nadir	0.03 ng/mL Interval 0.0 to 0.27	0.02 ng/mL Interval 0.0 to 0.14

Adverse Events

ARM 1

Serious events: 3 serious events

Other events: 50 other events

Deaths: 0 deaths

ARM 2

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ARM 1 n=50 participants at risk Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 participants at risk Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Respiratory, thoracic and mediastinal disorders Chylothorax	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Vascular disorders Hematoma	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Cardiac disorders Cardiac disorders - Other	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Vascular disorders Hot flashes	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
General disorders Pain	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Injury, poisoning and procedural complications Fracture	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Investigations Aspartate aminotransferase increased	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.

Other adverse events

Additional Information

Mary-Ellen Taplin, MD

Dana-Farber Cancer Institute

Phone: 617-582-7221

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	ARM 1 n=50 participants at risk Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Abiraterone Acetate: 1000 mg (four 250 mg tablets), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Prednisone: 5 mg, oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.	ARM 2 n=25 participants at risk Enzalutamide: 160 mg (four 40 mg capsules), oral, once daily, 28 days (4 weeks) 6 cycles maximum. Leuprolide Acetate: Either 7.5 mg monthly or 22.5 mg every three months, Intramuscular, monthly or every three months.
Gastrointestinal disorders Abdominal pain	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	12.0% 3/25 • Assessed over treatment duration of 24 weeks.
Investigations Alanine aminotransferase increased	34.0% 17/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Alopecia	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Blood and lymphatic system disorders Anemia	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Metabolism and nutrition disorders Anorexia	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Anxiety	8.0% 4/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Arthritis	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Investigations Aspartate aminotransferase increased	32.0% 16/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Cardiac disorders Atrial fibrillation	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Back pain	8.0% 4/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Infections and infestations Bladder infection	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Investigations Blood bilirubin increased	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Eye disorders Blurred vision	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Bone pain	8.0% 4/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Cardiac disorders Chest pain - cardiac	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Chest wall pain	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Investigations Cholesterol high	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Cognitive disturbance	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Concentration impairment	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Confusion	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Eye disorders Conjunctivitis	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Constipation	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Cough	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Depression	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	12.0% 3/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Diarrhea	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Dizziness	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Eye disorders Dry eye	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Dysgeusia	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Ear and labyrinth disorders Ear and labyrinth disorders - Other	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Endocrine disorders Endocrine disorders - Other	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Reproductive system and breast disorders Erectile dysfunction	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Eye disorders Eye disorders - Other	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
General disorders Fatigue	64.0% 32/50 • Assessed over treatment duration of 24 weeks.	64.0% 16/25 • Assessed over treatment duration of 24 weeks.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Flank pain	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Flatulence	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Vascular disorders Flushing	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Gastrointestinal disorders - Other	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
General disorders General disorders and administration site conditions - Other	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	12.0% 3/25 • Assessed over treatment duration of 24 weeks.
Reproductive system and breast disorders Gynecomastia	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	12.0% 3/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Hallucinations	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Headache	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	12.0% 3/25 • Assessed over treatment duration of 24 weeks.
Renal and urinary disorders Hematuria	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Hoarseness	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Vascular disorders Hot flashes	82.0% 41/50 • Assessed over treatment duration of 24 weeks.	88.0% 22/25 • Assessed over treatment duration of 24 weeks.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Vascular disorders Hypertension	34.0% 17/50 • Assessed over treatment duration of 24 weeks.	28.0% 7/25 • Assessed over treatment duration of 24 weeks.
Metabolism and nutrition disorders Hypertriglyceridemia	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Metabolism and nutrition disorders Hypokalemia	10.0% 5/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Metabolism and nutrition disorders Hyponatremia	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Metabolism and nutrition disorders Hypophosphatemia	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
General disorders Infusion related reaction	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Insomnia	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	16.0% 4/25 • Assessed over treatment duration of 24 weeks.
Investigations Investigations - Other	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
General disorders Irritability	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Lethargy	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Libido decreased	10.0% 5/50 • Assessed over treatment duration of 24 weeks.	16.0% 4/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Memory impairment	10.0% 5/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	10.0% 5/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Nausea	8.0% 4/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Nervous system disorders - Other	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Nervous system disorders - Other, specify	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Investigations Neutrophil count decreased	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
General disorders Non-cardiac chest pain	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
General disorders Pain	12.0% 6/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Cardiac disorders Palpitations	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Infections and infestations Papulopustular rash	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Paresthesia	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Peripheral sensory neuropathy	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Infections and infestations Pharyngitis	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Nervous system disorders Presyncope	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Psychiatric disorders - Other	12.0% 6/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Rash acneiform	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Rash maculo-papular	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Rectal hemorrhage	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Renal and urinary disorders Renal and urinary disorders - Other	8.0% 4/50 • Assessed over treatment duration of 24 weeks.	20.0% 5/25 • Assessed over treatment duration of 24 weeks.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Restlessness	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	8.0% 2/25 • Assessed over treatment duration of 24 weeks.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	8.0% 4/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Infections and infestations Skin infection	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Psychiatric disorders Suicidal ideation	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Reproductive system and breast disorders Testicular disorder	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Gastrointestinal disorders Tooth development disorder	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Infections and infestations Tooth infection	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Infections and infestations Upper respiratory infection	6.0% 3/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Renal and urinary disorders Urinary frequency	12.0% 6/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Renal and urinary disorders Urinary retention	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Infections and infestations Urinary tract infection	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Renal and urinary disorders Urinary urgency	4.0% 2/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Vascular disorders Vascular disorders - Other	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Ear and labyrinth disorders Vertigo	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Investigations Weight loss	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.
Respiratory, thoracic and mediastinal disorders Wheezing	2.0% 1/50 • Assessed over treatment duration of 24 weeks.	0.00% 0/25 • Assessed over treatment duration of 24 weeks.
Investigations White blood cell decreased	0.00% 0/50 • Assessed over treatment duration of 24 weeks.	4.0% 1/25 • Assessed over treatment duration of 24 weeks.