Trial Outcomes & Findings for PK/PD Pediatric ADHD Classroom Study (NCT NCT02536105)

Last Updated: 2019-12-10

Results Overview

The Permanent Product Measure of Performance (PERMP) involves objective individualized mathematics tests. Scores will be obtained ten times on each classroom day at pre-dose, and at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose. PERMP Attempted is reported here. Scale ranges 0 math questions answered to 400 math questions answered. The more number of questions answered (better score), the higher the PERMP Attempted score is.

Recruitment status

COMPLETED

Study phase

Target enrollment

88 participants

Primary outcome timeframe

0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day

Results posted on

2019-12-10

Participant Flow

88 individuals signed consent. 82 individuals were eligible for the study. 80 individuals were exposed to the open-label phase (Methylphenidate HCL ER Tablets 1). 76 individuals entered the double-blind phase. 72 individuals completed the entire study. Since this is a crossover study, these were the same individuals (88 consented, not 301).

Participant milestones

Participant milestones
Measure	All Participants Participants received 4 different medications at the following 5 time points. 1. Open-label phase MPH ER Tab 1 2. Crossover Placebo 3. Crossover MPH ER Tab 1 4. Crossover MPH ER Tab 2 5. Crossover MPH ER Suspension
Concerta Open Label STARTED	80
Concerta Open Label Completion of Phase	76
Concerta Open Label COMPLETED	72
Concerta Open Label NOT COMPLETED	8
Placebo STARTED	74
Placebo Completion of Placebo Day	74
Placebo COMPLETED	72
Placebo NOT COMPLETED	2
Methylphenidate HCl ER Tablet 1 STARTED	72
Methylphenidate HCl ER Tablet 1 Completion of MPH HCl ER Tab 1 Day	72
Methylphenidate HCl ER Tablet 1 COMPLETED	72
Methylphenidate HCl ER Tablet 1 NOT COMPLETED	0
Methylphenidate HCl ER Tablet 2 STARTED	73
Methylphenidate HCl ER Tablet 2 Completion of MPH HCl ER Tablet 2 Phase	73
Methylphenidate HCl ER Tablet 2 COMPLETED	72
Methylphenidate HCl ER Tablet 2 NOT COMPLETED	1
Methylphenidate HCl ER Suspension STARTED	74
Methylphenidate HCl ER Suspension Completion of MPH HCl ER Susp Phase	74
Methylphenidate HCl ER Suspension COMPLETED	72
Methylphenidate HCl ER Suspension NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

PK/PD Pediatric ADHD Classroom Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-Label: Methylphenidate HCl ER Tablets 1 n=80 Participants During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. Methylphenidate HCl ER tablets 1
Age, Categorical <=18 years	80 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	9.45 years STANDARD_DEVIATION 1.86 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants
Race (NIH/OMB) More than one race	16 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	80 participants n=5 Participants

PRIMARY outcome

Timeframe: 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day

Population: Note that not all participants who entered the study completed all arms and all time points, hence the discrepancy in number of participants analyzed between arms and different time points.

Outcome measures

Outcome measures
Measure	Methylphenidate HCl ER Tablets 1 n=67 Participants During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 1	Placebo n=72 Participants During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. Placebo	Methylphenidate HCl ER Tablets 2 n=66 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 2	Methylphenidate HCl ER for Suspension n=68 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER for suspension
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 0	66.925 score on a scale Standard Deviation 43.7199	95.361 score on a scale Standard Deviation 53.7921	80.621 score on a scale Standard Deviation 57.0923	92.176 score on a scale Standard Deviation 70.6378
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR .5	78.463 score on a scale Standard Deviation 58.8659	90.194 score on a scale Standard Deviation 67.6144	88.333 score on a scale Standard Deviation 73.9824	114.294 score on a scale Standard Deviation 76.9904
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 1.5	112.493 score on a scale Standard Deviation 62.1631	89.366 score on a scale Standard Deviation 74.0415	112.364 score on a scale Standard Deviation 70.9701	131.191 score on a scale Standard Deviation 65.958
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 2.5	124.313 score on a scale Standard Deviation 65.4757	86.236 score on a scale Standard Deviation 61.5375	127.848 score on a scale Standard Deviation 71.7946	139.132 score on a scale Standard Deviation 75.4724
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 4	120.985 score on a scale Standard Deviation 64.1158	85.986 score on a scale Standard Deviation 63.3276	130.591 score on a scale Standard Deviation 65.7204	129.735 score on a scale Standard Deviation 70.0097
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 5	103.985 score on a scale Standard Deviation 58.6211	71.718 score on a scale Standard Deviation 56.1392	117.879 score on a scale Standard Deviation 63.5952	122.91 score on a scale Standard Deviation 72.3134
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 6	107.303 score on a scale Standard Deviation 64.5355	73.42 score on a scale Standard Deviation 48.0843	112.985 score on a scale Standard Deviation 68.729	124.862 score on a scale Standard Deviation 68.9096
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 8	117.403 score on a scale Standard Deviation 66.8252	82.408 score on a scale Standard Deviation 59.657	123.803 score on a scale Standard Deviation 65.2423	97.358 score on a scale Standard Deviation 58.9822
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 10	113.03 score on a scale Standard Deviation 65.3686	80.761 score on a scale Standard Deviation 60.2045	103.864 score on a scale Standard Deviation 60.7101	99.881 score on a scale Standard Deviation 66.7032
Permanent Product Measure of Performance (PERMP) for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 12	112.09 score on a scale Standard Deviation 76.5476	82.718 score on a scale Standard Deviation 50.4251	109.909 score on a scale Standard Deviation 64.7206	82.642 score on a scale Standard Deviation 58.0224

PRIMARY outcome

Timeframe: 0.5, 1.5, 2.5, 4, 5, 6, 8, 10 and 12 hours post-dose on each classroom day

Population: Note that not all participants who entered the study completed all arms. Thus, the number differs between the arms to reflect the number of participants who provided data for that arm. N=67 for all MPH HCl ER tab 1 time points. N=72 for all placebo time points. N=66 for all MPH HCl tab 2 time points. N=68 for all MPH Hcl ER susp timepoints.

The Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scale is a validated, 13-item rating of subjective impairment of classroom behaviors (0 = normal/no impairment; 1 = slight impairment; 2 = mild impairment; 3 = moderate impairment; 4 = severe impairment; 5 = very severe impairment; 6 = maximal impairment). The SKAMP consists of four subscales: SKAMP-Attention, SKAMP-Deportment, SKAMP-Quality of Work, and SKAMP-Compliance, in addition to SKAMP-Total (reported here). SKAMP-Total is a sum of the four sub-scales and has a range of 0-78. The higher the score, the higher the impairment. Scores will be obtained during each classroom cycle during each full laboratory classroom day at pre-dose, and at 0.5, 1.5, 2.5, 4, 5, 6, 8, 10, and 12 hours post-dose. The scores will be based on the child's behavior during 20 minutes of each cycle.

Outcome measures

Outcome measures
Measure	Methylphenidate HCl ER Tablets 1 n=67 Participants During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 1	Placebo n=72 Participants During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. Placebo	Methylphenidate HCl ER Tablets 2 n=66 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 2	Methylphenidate HCl ER for Suspension n=68 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER for suspension
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 1.5	23.4328 units on a scale Standard Deviation 15.9917	33.9722 units on a scale Standard Deviation 15.354	25.4091 units on a scale Standard Deviation 13.8775	17.8676 units on a scale Standard Deviation 12.9233
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 10	20.7164 units on a scale Standard Deviation 13.313	34.2222 units on a scale Standard Deviation 14.0554	24.4394 units on a scale Standard Deviation 15.1679	31.9412 units on a scale Standard Deviation 13.7329
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 0	36.4328 units on a scale Standard Deviation 13.1209	27.7917 units on a scale Standard Deviation 13.475	34.2879 units on a scale Standard Deviation 14.4497	33.4706 units on a scale Standard Deviation 14.7855
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR .5	35.2836 units on a scale Standard Deviation 15.2204	30.7361 units on a scale Standard Deviation 14.8029	32.1061 units on a scale Standard Deviation 13.2875	27.0588 units on a scale Standard Deviation 16.1466
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 2.5	20.0746 units on a scale Standard Deviation 12.6087	33.4861 units on a scale Standard Deviation 13.2399	20.3939 units on a scale Standard Deviation 13.4163	15.8088 units on a scale Standard Deviation 10.9466
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 4	19.1642 units on a scale Standard Deviation 12.216	33.4028 units on a scale Standard Deviation 13.7888	15.7576 units on a scale Standard Deviation 10.5233	17.4412 units on a scale Standard Deviation 12.3462
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 5	22.3881 units on a scale Standard Deviation 12.7588	36.2917 units on a scale Standard Deviation 14.1962	17.1061 units on a scale Standard Deviation 11.9526	20.6765 units on a scale Standard Deviation 13.3108
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 6	22.1642 units on a scale Standard Deviation 12.8766	35.00 units on a scale Standard Deviation 14.7601	15.8636 units on a scale Standard Deviation 10.5158	22.8382 units on a scale Standard Deviation 14.8078
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 8	21.0448 units on a scale Standard Deviation 11.8186	35.0972 units on a scale Standard Deviation 14.4038	19.3788 units on a scale Standard Deviation 12.0509	28.3382 units on a scale Standard Deviation 14.6548
Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale for Three Methylphenidate Hydrochloride Extended-release Drug Products HOUR 12	23.0746 units on a scale Standard Deviation 15.3981	32.2778 units on a scale Standard Deviation 14.396	27.3485 units on a scale Standard Deviation 15.3508	34.7353 units on a scale Standard Deviation 15.3123

PRIMARY outcome

Timeframe: 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day

Population: 76 participants entered the double-blind randomization phase and each participant provided at least one data point for these analyses.

PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Cmax will be measured. The objectives of this measure is to estimate PK metrics, including Cmax, appropriate for characterizing rate and extent of absorption in each phase of the drug release and the evaluate the disposition and eliminating processes for each medication studied. The minimum value is pg/mL and there is was no maximum defined prior to the interventions.

Outcome measures

Outcome measures
Measure	Methylphenidate HCl ER Tablets 1 n=76 Participants During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 1	Placebo n=76 Participants During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. Placebo	Methylphenidate HCl ER Tablets 2 n=76 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 2	Methylphenidate HCl ER for Suspension n=76 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER for suspension
Maximum Drug Concentration Observed (Cmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products	76339 pg/mL Standard Deviation 55690	4327 pg/mL Standard Deviation 4594	81611 pg/mL Standard Deviation 46702	81498 pg/mL Standard Deviation 66961

PRIMARY outcome

Timeframe: 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose on each classroom day

Population: 76 participants entered the double-blind randomization phase and each participant provided at least one data point for these analyses.

PK samples will be taken eight times on each classroom day at approximately 0.5, 1.5, 2.5, 4, 5, 6, 8, and 12 hours post-dose, and Tmax will be measured

Outcome measures

Outcome measures
Measure	Methylphenidate HCl ER Tablets 1 n=76 Participants During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 1	Placebo n=76 Participants During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. Placebo	Methylphenidate HCl ER Tablets 2 n=76 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 2	Methylphenidate HCl ER for Suspension n=76 Participants During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER for suspension
Time to Reach Cmax (Tmax) for Three Methylphenidate Hydrochloride Extended-release Drug Products	7.35 Hours Standard Deviation 3.05	4.7 Hours Standard Deviation 2.99	6.35 Hours Standard Deviation 2.22	3.97 Hours Standard Deviation 2.19

Adverse Events

Methylphenidate HCl ER Tablets 1

Serious events: 0 serious events

Other events: 69 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Methylphenidate HCl ER Tablets 2

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Methylphenidate HCl ER for Suspension

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Thomas Spencer

Massachusetts General Hospital

Phone: 617-724-5600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Methylphenidate HCl ER Tablets 1 n=80 participants at risk During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 1	Placebo n=74 participants at risk During the double-blind period, in one of the 4 study weeks, the study participant will take a blinded placebo instead of one of the the 3 active comparators. Placebo	Methylphenidate HCl ER Tablets 2 n=73 participants at risk During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER tablets 2	Methylphenidate HCl ER for Suspension n=74 participants at risk During the open-label optimization phase, one of the methylphenidate hydrochloride extended-release products will be titrated at weekly intervals of 18mg increments until an optimal dose is achieved or a maximum of 72mg per day is reached. During the double-blind phase, participants will receive blinded treatment each week. The dose of each methylphenidate hydrochloride extended-release product will be determined by the optimized dose during the open-label optimization phase Methylphenidate HCl ER for suspension
Psychiatric disorders Insomnia	38.8% 31/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	4.1% 3/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Gastrointestinal disorders Low Appetite	51.2% 41/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	5.5% 4/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	5.4% 4/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Psychiatric disorders Emotional Lability	25.0% 20/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	5.5% 4/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	4.1% 3/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Infections and infestations Upper Respiratory Infection	12.5% 10/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Gastrointestinal disorders GI Distress	11.2% 9/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	4.1% 3/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Gastrointestinal disorders Abdominal Pain	25.0% 20/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	4.1% 3/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Gastrointestinal disorders Vomited	8.8% 7/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Nervous system disorders Headache	20.0% 16/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	4.1% 3/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Psychiatric disorders Anger/Aggression/Oppositional Behavior	7.5% 6/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Psychiatric disorders Dysphoria/Anxiety	2.5% 2/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Gastrointestinal disorders Diarrhea	5.0% 4/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Gastrointestinal disorders Constipation	2.5% 2/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Blood and lymphatic system disorders Epistaxis	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Musculoskeletal and connective tissue disorders Ankle Pain/Strain	0.00% 0/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Respiratory, thoracic and mediastinal disorders Strep Throat/Sore Throat	3.8% 3/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Respiratory, thoracic and mediastinal disorders Cough	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	2.7% 2/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Immune system disorders Influenza	2.5% 2/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Nervous system disorders Motor Tics	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Skin and subcutaneous tissue disorders Rash	3.8% 3/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Skin and subcutaneous tissue disorders Bug Bites/Bee Stings	2.5% 2/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Ear and labyrinth disorders Otitis Media/Ear Pain	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Immune system disorders Carious Teeth	0.00% 0/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Endocrine disorders Growth Hormone Deficiency	0.00% 0/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Musculoskeletal and connective tissue disorders Muscle Strain/Pain	7.5% 6/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	1.4% 1/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Skin and subcutaneous tissue disorders Cellulitis	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Infections and infestations Mouth Ulcers/Bad Breath	2.5% 2/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Respiratory, thoracic and mediastinal disorders Dry Mouth	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Eye disorders Eye Pain	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Skin and subcutaneous tissue disorders Sunburn	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Metabolism and nutrition disorders Weight Loss	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Injury, poisoning and procedural complications Foreign Body Swallowed	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Skin and subcutaneous tissue disorders Finger Laceration	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Social circumstances Flat Affect	2.5% 2/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Renal and urinary disorders Urinary Tract Infection	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Nervous system disorders Dizziness	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Musculoskeletal and connective tissue disorders Toe Fracture	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Cardiac disorders Heart Palpitations	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.
Psychiatric disorders Staring Episodes	1.2% 1/80 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/73 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.	0.00% 0/74 • Baseline (Week 0) to Visit 14 (Week 12) or Drop Visit Adverse events were collected during the entirety of the study, from consent to completion or withdrawal from the study.