Trial Outcomes & Findings for Evaluation of Food Effect on Pharmacokinetics of Vismodegib (NCT NCT01174264)

Last Updated: 2017-05-19

Results Overview

Highest observed concentration over the 168 hour period. Blood samples were collected at j0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 24, 48, 120, and 168 hours.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

63 participants

Primary outcome timeframe

168 hours

Results posted on

2017-05-19

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (Vismodegib on Empty Stomach) Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Single Dose Pharmacokinetics STARTED	23	20	20
Single Dose Pharmacokinetics COMPLETED	22	20	18
Single Dose Pharmacokinetics NOT COMPLETED	1	0	2
Steady-state Pharmacokinetics STARTED	31	0	29
Steady-state Pharmacokinetics COMPLETED	25	0	27
Steady-state Pharmacokinetics NOT COMPLETED	6	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Vismodegib on Empty Stomach) Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Single Dose Pharmacokinetics Early progressive disease	1	1
Single Dose Pharmacokinetics Patient entered hospice care	0	1
Steady-state Pharmacokinetics Not evaluable	6	2

Baseline Characteristics

Evaluation of Food Effect on Pharmacokinetics of Vismodegib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Vismodegib on Empty Stomach) n=23 Participants Patients receive a single dose of vismodegib PO on an empty stomach. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) n=20 Participants Patients receive a single dose of vismodegib PO after eating a high fat meal. Beginning 7 days later, patients receive vismodegib PO on an empty stomach daily on days 1-28. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=20 Participants Patients receive a single dose of vismodegib PO after eating a low fat meal. Beginning 7 days later, patients receive vismodegib PO after eating a meal daily on days 1-28. Pharmacological Study: Correlative studies Vismodegib: Given PO	Total n=63 Participants Total of all reporting groups
Age, Continuous	53 years n=99 Participants	57 years n=107 Participants	64 years n=206 Participants	61 years n=7 Participants
Sex: Female, Male Female	15 Participants n=99 Participants	11 Participants n=107 Participants	14 Participants n=206 Participants	40 Participants n=7 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	9 Participants n=107 Participants	6 Participants n=206 Participants	23 Participants n=7 Participants
Race/Ethnicity, Customized White	16 participants n=99 Participants	17 participants n=107 Participants	16 participants n=206 Participants	49 participants n=7 Participants
Race/Ethnicity, Customized African-American	6 participants n=99 Participants	3 participants n=107 Participants	2 participants n=206 Participants	11 participants n=7 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=99 Participants	0 participants n=107 Participants	2 participants n=206 Participants	3 participants n=7 Participants
Region of Enrollment United States	23 participants n=99 Participants	20 participants n=107 Participants	20 participants n=206 Participants	63 participants n=7 Participants

PRIMARY outcome

Timeframe: 168 hours

Highest observed concentration over the 168 hour period. Blood samples were collected at j0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 24, 48, 120, and 168 hours.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=22 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) n=20 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=18 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Cmax Following Single Dose of Drug	3244 ng/ml Geometric Coefficient of Variation 55	5666 ng/ml Geometric Coefficient of Variation 45	3511 ng/ml Geometric Coefficient of Variation 40

PRIMARY outcome

Timeframe: 168 hours

Area under the curve from 0-168 hours.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=22 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) n=20 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=18 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
AUC Following Single Dose of Drug	416635 ng*h/mL Geometric Coefficient of Variation 56	723822 ng*h/mL Geometric Coefficient of Variation 54	466566 ng*h/mL Geometric Coefficient of Variation 38

PRIMARY outcome

Timeframe: 168 hours

Time of maximum drug concentration

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=22 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) n=20 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=18 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Tmax'Following Single Dose of Drug	57 hours Standard Deviation 62	44 hours Standard Deviation 48	62 hours Standard Deviation 57

PRIMARY outcome

Timeframe: 168 hours

Time between drug administration and when it is first observed in the systemic circulation.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=22 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) n=20 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=18 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Tlag Following Single Dose of Drug	0.11 hours Standard Deviation 0.17	0.50 hours Standard Deviation 0.29	0.58 hours Standard Deviation 0.45

PRIMARY outcome

Timeframe: 24 hours

Minimum blood concentration over 24-hour observation period. Blood sample collected at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 24 hours.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=25 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=27 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Ctrough Following Steady State Exposure for 14 Days	10493 ng/ml Geometric Coefficient of Variation 37	—	12171 ng/ml Geometric Coefficient of Variation 35

PRIMARY outcome

Timeframe: 24 hours

Maximum drug concentration over 24 hours.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=25 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=27 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Cmax Following Steady State Exposure for 14 Days	11449 ng/ml Geometric Coefficient of Variation 37	—	12950 ng/ml Geometric Coefficient of Variation 34

PRIMARY outcome

Timeframe: 24 hours

Population: 3 and 2 patients with missing data, respectively

Area under the curve from 0 to 24 hours.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=22 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=25 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
AUC Following Steady State Exposure for 14 Days	238740 ng*h/mL Geometric Coefficient of Variation 40	—	290896 ng*h/mL Geometric Coefficient of Variation 35

PRIMARY outcome

Timeframe: 24 hours

Time of maximum drug concentration.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=25 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=27 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Tmax Following Steady State Exposure for 14 Days	6.7 hours Standard Deviation 9.1	—	10.2 hours Standard Deviation 10.3

SECONDARY outcome

Timeframe: Up to 30 days

Population: 2 patients in Arm I and 4 patients in Arm III were non-evaluable for response.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Arm I (Vismodegib on Empty Stomach) n=23 Participants Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=23 Participants Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Objective Responses in Patients With Solid Tumors	1 participants	—	0 participants

Adverse Events

Arm I (Vismodegib on Empty Stomach)

Serious events: 15 serious events

Other events: 31 other events

Deaths: 0 deaths

Arm II (Vismodegib After High Fat Meal)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm III (Vismodegib After Low Fat Meal)

Serious events: 14 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Theodore Karrison

University of Chicago

Phone: 773-702-9326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Arm I (Vismodegib on Empty Stomach) n=31 participants at risk Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=30 participants at risk Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Gastrointestinal disorders Abdominal pain	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Alanine aminotransferase increased	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Blood and lymphatic system disorders Anemia	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Aspartate aminotransferase increased	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Respiratory, thoracic and mediastinal disorders Atelectasis	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Blood bilirubin increased	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Cardiac disorders Chest pain - cardiac	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Colonic obstruction	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Death NOS	16.1% 5/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	10.0% 3/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Psychiatric disorders Delirium	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Nervous system disorders Dizziness	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.1% 5/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	16.7% 5/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Reproductive system and breast disorders Erectile dysfunction	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Fatigue	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Renal and urinary disorders Hematuria	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hypercalcemia	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hyponatremia	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Lymphocyte count decreased	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Nervous system disorders Memory impairment	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Nausea	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Neutrophil count decreased	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Non-cardiac chest pain	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Pain	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Cardiac disorders Paroxysmal atrial tachycardia	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Infections and infestations Skin infection	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	3.3% 1/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Stomach pain	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Vascular disorders Thromboembolic event	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Ear and labyrinth disorders Vertigo	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Vomiting	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.

Other adverse events
Measure	Arm I (Vismodegib on Empty Stomach) n=31 participants at risk Patients receive a single dose (150 mg) of vismodegib PO on an empty stomach. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm II (Vismodegib After High Fat Meal) Patients receive a single dose (150 mg) of vismodegib PO after eating a high fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO	Arm III (Vismodegib After Low Fat Meal) n=30 participants at risk Patients receive a single dose (150 mg) of vismodegib PO after eating a low fat meal. 7 days later, patients received 150 mg daily for 28 days. Pharmacological Study: Correlative studies Vismodegib: Given PO
Gastrointestinal disorders Abdominal pain	12.9% 4/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	16.7% 5/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Alanine aminotransferase increased	12.9% 4/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	26.7% 8/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Alkaline phosphatase increased	29.0% 9/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	16.7% 5/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Skin and subcutaneous tissue disorders Alopecia	16.1% 5/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	10.0% 3/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Blood and lymphatic system disorders Anemia	45.2% 14/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	33.3% 10/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Anorexia	48.4% 15/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	46.7% 14/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Musculoskeletal and connective tissue disorders Arthralgia	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	10.0% 3/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Aspartate aminotransferase increased	19.4% 6/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	16.7% 5/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Musculoskeletal and connective tissue disorders Back pain	12.9% 4/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	20.0% 6/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Bloating	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Blood bilirubin increased	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	16.7% 5/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Chills	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Constipation	12.9% 4/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	26.7% 8/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Respiratory, thoracic and mediastinal disorders Cough	16.1% 5/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	13.3% 4/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Investigations Creatinine increased	12.9% 4/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	10.0% 3/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Psychiatric disorders Depression	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Diarrhea	22.6% 7/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	13.3% 4/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Nervous system disorders Dizziness	12.9% 4/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	13.3% 4/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Dry mouth	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Nervous system disorders Dysgeusia	25.8% 8/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	43.3% 13/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnea	25.8% 8/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	26.7% 8/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Ear and labyrinth disorders Ear pain	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Edema limbs	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	13.3% 4/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Reproductive system and breast disorders Erectile dysfunction	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Injury, poisoning and procedural complications Fall	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Fatigue	41.9% 13/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	50.0% 15/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Fever	12.9% 4/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Musculoskeletal and connective tissue disorders Flank pain	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
General disorders Flu like symptoms	0.00% 0/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Gastrointestinal disorders Gastrointestinal disorders - Other	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	3.2% 1/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	10.0% 3/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Nervous system disorders Headache	16.1% 5/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	10.0% 3/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hypercalcemia	6.5% 2/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hyperglycemia	54.8% 17/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	40.0% 12/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hyperkalemia	22.6% 7/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	16.7% 5/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hypernatremia	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	6.7% 2/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hypoalbuminemia	25.8% 8/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	26.7% 8/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hypocalcemia	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	16.7% 5/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.
Metabolism and nutrition disorders Hypokalemia	9.7% 3/31 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	— 0/0 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.	0.00% 0/30 • Up to 3 years. Includes all patients who received at least one dose in the daily dosing phase of the study. Recorded are adverse events of any grade level, whether or not attributable to the study drug.