Trial Outcomes & Findings for Curcumin in Treating Patients With Familial Adenomatous Polyposis (NCT NCT00641147)

Results Overview

Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2017-09-29

Participant Flow

Subjects were screened and enrolled at the Johns Hopkins Hospital and the University of Puerto Rico Hospital.

Participant milestones

Participant milestones
Measure	Arm I (Curcumin) Patients receive curcumin by mouth (PO) twice a day (BID) for 12 months. Curcumin: Given PO	Arm II (Placebo) Patients receive placebo PO BID for 12 months. Placebo: Given PO
Completed 4 Months. STARTED	21	23
Completed 4 Months. COMPLETED	19	23
Completed 4 Months. NOT COMPLETED	2	0
Completed 8 Months. STARTED	19	23
Completed 8 Months. COMPLETED	16	21
Completed 8 Months. NOT COMPLETED	3	2
Completed 12 Months. STARTED	16	21
Completed 12 Months. COMPLETED	15	19
Completed 12 Months. NOT COMPLETED	1	2
Completed 16 Months. STARTED	15	19
Completed 16 Months. COMPLETED	13	19
Completed 16 Months. NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I (Curcumin) Patients receive curcumin by mouth (PO) twice a day (BID) for 12 months. Curcumin: Given PO	Arm II (Placebo) Patients receive placebo PO BID for 12 months. Placebo: Given PO
Completed 4 Months. Physician Decision	1	0
Completed 4 Months. Adverse Event	1	0
Completed 8 Months. Physician Decision	2	1
Completed 8 Months. non compliance	1	0
Completed 8 Months. Withdrawal by Subject	0	1
Completed 12 Months. Physician Decision	1	1
Completed 12 Months. Withdrawal by Subject	0	1
Completed 16 Months. Physician Decision	1	0
Completed 16 Months. Lost to Follow-up	1	0

Baseline Characteristics

Curcumin in Treating Patients With Familial Adenomatous Polyposis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO	Total n=44 Participants Total of all reporting groups
Age, Continuous	44.5 years STANDARD_DEVIATION 15.4 • n=93 Participants	38.7 years STANDARD_DEVIATION 15.0 • n=4 Participants	41.5 years STANDARD_DEVIATION 15.3 • n=27 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	14 Participants n=4 Participants	28 Participants n=27 Participants
Sex: Female, Male Male	7 Participants n=93 Participants	9 Participants n=4 Participants	16 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=93 Participants	11 Participants n=4 Participants	22 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=93 Participants	12 Participants n=4 Participants	22 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) White	21 Participants n=93 Participants	22 Participants n=4 Participants	43 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Baseline number of polyps	23.3 polyps STANDARD_DEVIATION 19.7 • n=93 Participants	18.7 polyps STANDARD_DEVIATION 13.1 • n=4 Participants	20.9 polyps STANDARD_DEVIATION 16.6 • n=27 Participants
Baseline size of polyps in mm	3.1 polyps STANDARD_DEVIATION 1.7 • n=93 Participants	2.3 polyps STANDARD_DEVIATION 0.6 • n=4 Participants	2.6 polyps STANDARD_DEVIATION 1.3 • n=27 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Average number of polyps in the placebo arm at the end of the study is compared to the average in the curcumin arm

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=16 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=21 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Polyp Number	22.6 polyps Interval 12.1 to 33.1	18.6 polyps Interval 9.3 to 27.8

SECONDARY outcome

Timeframe: Up to 12 months

Mean size of the 5 largest polyps

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=16 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=21 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Mean Polyp Size in mm	2.3 mm Interval 1.6 to 3.0	2.1 mm Interval 1.5 to 2.7

SECONDARY outcome

Timeframe: 12 months

The polyp burden as evaluated by video tape review. Polyp burden at 12 months compared to time 0 for each participant and counting participants with decrease in polyp burden at 12 months.

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=15 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=19 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Number of Participants With a Decrease in Polyp Burden at 12 Months	4 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Events were graded as follows: Grade 0= no adverse event or within normal limits; Grade 1= mild adverse event (causing no limitations of usual activity); Grade 2= moderate adverse event (causing some limitation of activity); Grade 3= severe adverse event (severe and undesirable; causing inability to carry out usual activities; Grade 4= life threatening or disabling adverse event; Grade 5= fatal adverse event.

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Number of Participants With Grade >=2 Adverse Events	6 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 12 months

Medication compliance of the participant= number of capsules taken divided by the number of capsules prescribed as determined by pill count and described as a percentage per participant. Then the compliance of each participant in the assigned group (curcumin or placebo) was averaged together to obtain the medication compliance rate of that group.

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=19 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Medication Compliance	0.83 percentage of total compliance Interval 0.7 to 0.94	0.91 percentage of total compliance Interval 0.78 to 0.96

SECONDARY outcome

Timeframe: Baseline and 8 months

Change in ODC mean activity levels (expressed as nmol of activity/mg of mucosal tissue/hr) at 8 months compared to baseline (time 0)

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Change in Ornithine Decarboxylase (ODC) Activity Levels	1.19 nmol/mg/hr Standard Deviation 0.71	0.88 nmol/mg/hr Standard Deviation 1.58

SECONDARY outcome

Timeframe: Baseline and 8 months

Polyamine mean level changes (expressed as pg/mg protein) at month 8-baseline

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Change in Total Polyamines Levels	0.23 pg/mg protein Standard Deviation 3.41	1.66 pg/mg protein Standard Deviation 3.69

SECONDARY outcome

Timeframe: Baseline and 8 months

Change in MicroRNA mean activity level at 8 months compared to baseline (time 0)

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Change in Micro RNA 124-U6 (miR124-U6)	1.44 qRT-PCR relative to U6 snRNA Standard Deviation 1.08	4.88 qRT-PCR relative to U6 snRNA Standard Deviation 11.55

SECONDARY outcome

Timeframe: Baseline and 8 months

Change in SSAT mean activity level at 8 months compared to baseline (time 0)

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Change in Spermidine/Spermine N-1 Acetyl Transferase (SSAT)	0.97 pmol/acetylspermidine/mg protein/min Standard Deviation 0.51	0.99 pmol/acetylspermidine/mg protein/min Standard Deviation 0.56

SECONDARY outcome

Timeframe: Baseline and 8months

Change in SMOX mean activity level at 8 months compared to baseline (time 0)

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Change in Spermine Oxidase (SMOX)	1.20 pmol H2O2 per min per mg protein Standard Deviation 0.57	1.56 pmol H2O2 per min per mg protein Standard Deviation 2.36

SECONDARY outcome

Timeframe: Baseline up to 8 months

Population: Specimens for analysis were only available on 7 curcumin and 10 placebo participants.

Change in cellular proliferation rate was measured by assessment of Ki-67 anti-proliferative cell nuclear antibody index levels at 8 months

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=7 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=10 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Change in Ki-67 Anti-proliferative Cell Nuclear Antibody Index Levels	0.47 labeled cells/crypt epithelial cells Standard Deviation 0.21	0.41 labeled cells/crypt epithelial cells Standard Deviation 0.10

SECONDARY outcome

Timeframe: 8 months

Population: Specimens for analysis were only available on 7 curcumin and 10 placebo participants.

Change in apoptosis index levels at 8 months by assessing cleaved Caspase-3 measurement

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=7 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=10 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Change in Apoptosis Index Levels	0.57 apoptotic rate Standard Deviation 0.98	2.44 apoptotic rate Standard Deviation 2.74

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 12 months

Population: The outcome data were not collected and the outcome will never be analyzed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 12 months.

Population: The outcome data were not collected and the outcome will never be analyzed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 12 months.

Population: The outcome data were not collected and the outcome will never be analyzed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 16 months.

Patients withdrawn from study due to increasing polyp burden and/or advancing histology.

Outcome measures

Outcome measures
Measure	Arm I (Curcumin) n=21 Participants Patients receive curcumin 3.0 grams PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 Participants Patients receive placebo PO BID for 12 months. Placebo: Given PO
Number of Patients Failing Study.	1 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 12 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to 12 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 12 months

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Curcumin)

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Arm II (Placebo)

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (Curcumin) n=21 participants at risk Patients receive curcumin PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 participants at risk Patients receive placebo PO BID for 12 months. Placebo: Given PO
Gastrointestinal disorders Abdominal pain	9.5% 2/21 • Number of events 2 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Skin and subcutaneous tissue disorders Facial abscess	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Psychiatric disorders Depression	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.

Other adverse events

Additional Information

Study Coordinator

Johns Hopkins University

Phone: 410-955-3817

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm I (Curcumin) n=21 participants at risk Patients receive curcumin PO BID for 12 months. Curcumin: Given PO	Arm II (Placebo) n=23 participants at risk Patients receive placebo PO BID for 12 months. Placebo: Given PO
Gastrointestinal disorders Abdominal pain	14.3% 3/21 • Number of events 5 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	13.0% 3/23 • Number of events 3 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Gastrointestinal disorders Diarrhea	9.5% 2/21 • Number of events 2 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	8.7% 2/23 • Number of events 2 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Gastrointestinal disorders Nausea	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Blood and lymphatic system disorders Iron deficiency anemia	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Skin and subcutaneous tissue disorders Pruritus	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Skin and subcutaneous tissue disorders Cellulitis	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Skin and subcutaneous tissue disorders Herpes Zoster	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid Cancer	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Vascular disorders Headache migraine	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Respiratory, thoracic and mediastinal disorders Sinusitis	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Infections and infestations Facial abscess	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Infections and infestations Influenza	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Infections and infestations Viral infection	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Renal and urinary disorders Urinary tract infection	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Musculoskeletal and connective tissue disorders Back strain	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Musculoskeletal and connective tissue disorders Plantar fascilitis	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Musculoskeletal and connective tissue disorders Torn ligament	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Metabolism and nutrition disorders Gout	4.8% 1/21 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	0.00% 0/23 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.
Psychiatric disorders Depression	0.00% 0/21 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.	4.3% 1/23 • Number of events 1 • Reported adverse events (AE) included events starting on or after day 0 and on or before month 16. If a subject experienced more than 1 of a given AE the subject is counted only once for that AE. If a subject experienced more than 1 AE in a system organ class the subject is only counted once.