Trial Outcomes & Findings for Exploratory Study of TAC-302 in Detrusor Underactivity Patients With Overactive Bladder. (NCT NCT03175029)
NCT ID: NCT03175029
Last Updated: 2025-01-20
Results Overview
BCI indicates maxim um detrusor pressure at peak urine flow (PdetQmax) + 5 × peak urine flow rate (Qmax): PdetQmax and Qmax denotes detrusor pressure at maximum flow and maximum flow rate in pressure flow study, respectively. This index is used to assess detrusor contractility in men, with a higher value indicating greater detrusor contractility. Contractility can be divided into strong \> 150, normal 100-150, and weak \< 100. No theoretical minimum and maximum value of the scale range exists.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
195 participants
Primary outcome timeframe
Baseline to Week 12
Results posted on
2025-01-20
Participant Flow
This study was conducted at 21 medical institutions in Japan and the study period was from September 9, 2017 to November 14, 2019. Of the 213 patients who gave informed consent and received screening tests, 18 patients were withdrawn at screening. The number of patients enrolled in the observation period was 195 patients, but after the end of the observation period, 76 patients were determined to be eligible for enrollment in the treatment period.
Participant milestones
| Measure |
TAC-302
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
52
|
24
|
|
Overall Study
COMPLETED
|
49
|
23
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
| Measure |
TAC-302
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
1
|
|
Overall Study
Study treatment becomes impossible due to changing hospital or other reasons
|
1
|
0
|
Baseline Characteristics
This analysis was conducted only in male patients.
Baseline characteristics by cohort
| Measure |
TAC-302
n=42 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=18 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74.0 years
n=42 Participants
|
73.5 years
n=18 Participants
|
74.0 years
n=60 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=42 Participants
|
7 Participants
n=18 Participants
|
22 Participants
n=60 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=42 Participants
|
11 Participants
n=18 Participants
|
38 Participants
n=60 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=42 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Asian
|
42 Participants
n=42 Participants
|
18 Participants
n=18 Participants
|
60 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=42 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=42 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=42 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=42 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=42 Participants
|
0 Participants
n=18 Participants
|
0 Participants
n=60 Participants
|
|
Duration of lower urinary tract symptoms
|
79.0 months
n=42 Participants
|
45.5 months
n=18 Participants
|
68.0 months
n=60 Participants
|
|
Bladder voiding efficiency (BVE)
|
65.15 %
n=42 Participants
|
73.46 %
n=18 Participants
|
69.18 %
n=60 Participants
|
|
Bladder contractility index (BCI) (Only Male)
|
68.000 Score on a scale
n=27 Participants • This analysis was conducted only in male patients.
|
60.000 Score on a scale
n=11 Participants • This analysis was conducted only in male patients.
|
68.000 Score on a scale
n=38 Participants • This analysis was conducted only in male patients.
|
|
Projected isovolumetric pressure 1 (PIP1) (Only Female)
|
17.000 Score on a scale
n=15 Participants • This analysis was conducted only in female patients.
|
21.000 Score on a scale
n=7 Participants • This analysis was conducted only in female patients.
|
17.875 Score on a scale
n=22 Participants • This analysis was conducted only in female patients.
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: PPS was used for the analysis. This analysis was conducted only in male patients in the PPS.
BCI indicates maxim um detrusor pressure at peak urine flow (PdetQmax) + 5 × peak urine flow rate (Qmax): PdetQmax and Qmax denotes detrusor pressure at maximum flow and maximum flow rate in pressure flow study, respectively. This index is used to assess detrusor contractility in men, with a higher value indicating greater detrusor contractility. Contractility can be divided into strong \> 150, normal 100-150, and weak \< 100. No theoretical minimum and maximum value of the scale range exists.
Outcome measures
| Measure |
TAC-302
n=27 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=11 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Changes in the Mean BCI for Male From Baseline to Week 12
BCI at baseline
|
64.604 Score on a scale
Standard Deviation 16.569
|
61.339 Score on a scale
Standard Deviation 16.629
|
|
Changes in the Mean BCI for Male From Baseline to Week 12
BCI at Week 12
|
75.156 Score on a scale
Standard Deviation 21.076
|
60.513 Score on a scale
Standard Deviation 16.708
|
PRIMARY outcome
Timeframe: Baseline to Week 12Population: PPS was used for the analysis. This analysis was conducted only in female patients in the PPS.
PIP1 indicates PdetQma x + Qmax: PdetQmax and Qmax denotes detrusor pressure at maximum flow and maximum flow rate in pressure flow study, respectively. This index is used to assess detrusor contractility in women, with a higher value indicating greater detrusor contractility. Contractility can be divided into strong \> 75, normal 30-75, and weak \< 30. No theoretical minimum and maximum value of the scale range exists.
Outcome measures
| Measure |
TAC-302
n=15 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=7 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Changes in the Mean PIP1 for Female From Baseline to Week 12
PIP1 at baseline
|
18.769 Score on a scale
Standard Deviation 6.591
|
20.561 Score on a scale
Standard Deviation 7.524
|
|
Changes in the Mean PIP1 for Female From Baseline to Week 12
PIP1 at Week 12
|
29.373 Score on a scale
Standard Deviation 9.369
|
25.487 Score on a scale
Standard Deviation 9.581
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: FAS was used for the analysis. Therefore, the values presented here differ from those in the Baseline Characteristics module based on PPS.
BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Changes in the Mean BVE From Baseline to Week 12 (Overall)
BVE at Week 12
|
66.79 percentage
Standard Deviation 27.04
|
65.69 percentage
Standard Deviation 28.98
|
|
Changes in the Mean BVE From Baseline to Week 12 (Overall)
BVE at baseline
|
55.43 percentage
Standard Deviation 26.82
|
63.71 percentage
Standard Deviation 21.80
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: FAS was used for the analysis. Therefore, the values presented here differ from those in the Baseline Characteristics module based on PPS. This analysis was conducted in the subgroup of patients with post void residual ≥ 50 mL at baseline in the FAS.
BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.
Outcome measures
| Measure |
TAC-302
n=32 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=15 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Changes in the Mean BVE From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 50 mL at Baseline)
BVE at baseline
|
42.77 percentage
Standard Deviation 24.66
|
55.95 percentage
Standard Deviation 23.70
|
|
Changes in the Mean BVE From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 50 mL at Baseline)
BVE at Week 12
|
61.66 percentage
Standard Deviation 30.45
|
58.83 percentage
Standard Deviation 26.15
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: FAS was used for the analysis. Therefore, the values presented here differ from those in the Baseline Characteristics module based on PPS. This analysis was conducted In the subgroup of patients with post void residual ≥ 100 mL at baseline in the FAS.
BVE indicates Voided volume / (voided volume + post void residual): calculated from the voided volume measured by uroflowmetry and the post void residual measured by ultrasonography.
Outcome measures
| Measure |
TAC-302
n=22 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=10 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Changes in the Mean BVE for Female From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 100 mL at Baseline)
BVE at baseline
|
32.10 percentage
Standard Deviation 20.16
|
44.03 percentage
Standard Deviation 19.42
|
|
Changes in the Mean BVE for Female From Baseline to Week 12 (In the Subgroup of Patients With Post Void Residual ≥ 100 mL at Baseline)
BVE at Week 12
|
54.71 percentage
Standard Deviation 33.78
|
46.13 percentage
Standard Deviation 18.72
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: FAS was used for the analysis.
On the basis of information from bladder diary records in the 3 days directly before each evaluation timepoint, an average of urinations per 24 hours was calculated. The patients with at least 8 urinations per 24 hours at registration were included in this study.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Micturitions Per 24 Hours at Baseline and Week 12
Number of micturitions per 24 hours at baseline
|
11.753 Events
Standard Deviation 3.065
|
11.764 Events
Standard Deviation 3.145
|
|
Number of Micturitions Per 24 Hours at Baseline and Week 12
Number of micturitions per 24 hours at Week 12
|
10.830 Events
Standard Deviation 3.950
|
10.174 Events
Standard Deviation 2.348
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: FAS was used for the analysis.
On the basis of information from bladder diary records in the 3 days directly before each evaluation timepoint, an average of urinary urgency episodes per 24 hours was calculated. The patients with at least one urinary urgency episode per 24 hours at registration were included in this study.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Urinary Urgency Episodes Per 24 Hours at Baseline and Week 12
Number of urinary urgency episodes per 24 hours at baseline
|
5.452 Events
Standard Deviation 4.574
|
5.701 Events
Standard Deviation 3.878
|
|
Number of Urinary Urgency Episodes Per 24 Hours at Baseline and Week 12
Number of urinary urgency episodes per 24 hours at Week 12
|
4.469 Events
Standard Deviation 6.095
|
2.493 Events
Standard Deviation 3.600
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: FAS was used for the analysis.
Overactive bladder symptoms were evaluated using the OABSS. The OABSS Total Score is the sum of four symptom scores: daytime frequency (score 0-2), nighttime frequency (score 0-3), urgency (score 0-5), and urgency incontinence (score 0-5). The range of scores is from 0 to 15 points with a higher score indicating greater severity. A score ≤ 5 was determined to be mild, a score of 6 to 11 was determined to be moderate and a score ≥ 12 was determined to be severe.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Overactive Bladder Symptom Score (OABSS) Total Score at Baseline and Week 12
OABSS total score at baseline
|
8.7 points
Standard Deviation 2.9
|
8.9 points
Standard Deviation 2.4
|
|
Overactive Bladder Symptom Score (OABSS) Total Score at Baseline and Week 12
OABSS total score at Week 12
|
6.5 points
Standard Deviation 3.2
|
7.3 points
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)Population: All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events
Any adverse events
|
24 Participants
|
9 Participants
|
|
Number of Participants With Adverse Events
Deafness neurosensory
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Constipation
|
1 Participants
|
2 Participants
|
|
Number of Participants With Adverse Events
Dental caries
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Diarrhea
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Diverticulum intestinal haemorrhagic
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Glossitis
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Haematochezia
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Nausea
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Vomiting
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Pyrexia
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Bacteriuria
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Bronchitis
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Cystitis
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Miliaria
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Rash
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Orthostatic hypotension
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Gastroenteritis
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Herpes virus infection
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Influenza
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Nasopharyngitis
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Periodontitis
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Pharyngitis
|
1 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Pyuria
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Urinary tract infection
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Vulvitis
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Enteritis infectious
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Enterocolitis viral
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Compression fracture
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Fracture
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Subdural haematoma
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Contusion
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Post procedural haematuria
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Meniscus injury
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Tooth dislocation
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Blood creatinine phosphokinase increased
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Back pain
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Pain in extremity
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Headache
|
2 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Dysuria
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Renal colic
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Urethral pain
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Prostatitis
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events
Cough
|
0 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events
Dermatitis contact
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)Population: All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Drug Reactions
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)Population: All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Participants With Serious Adverse Events
Any serious adverse events
|
2 Participants
|
1 Participants
|
|
Number of Participants With Serious Adverse Events
Prostatitis
|
1 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events
Subdural haematoma
|
1 Participants
|
0 Participants
|
|
Number of Participants With Serious Adverse Events
Diverticulum intestinal haemorrhagic
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)Population: All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events Leading to Death
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)Population: All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events Leading to Dose Discontinuation
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)Population: All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
In tabulation of adverse events, the diagnoses entered on eCRFs were coded using the medical dictionary for regulatory activities (MedDRA) ver.22.1, and were presented as MedDRA preferred terms.
Outcome measures
| Measure |
TAC-302
n=52 Participants
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 Participants
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events Leading to Dose Interruption
Any adverse events leading to dose interruption
|
2 Participants
|
1 Participants
|
|
Number of Participants With Adverse Events Leading to Dose Interruption
Enteritis infectious
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Leading to Dose Interruption
Enterocolitis viral
|
1 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events Leading to Dose Interruption
Diverticulum intestinal haemorrhagic
|
0 Participants
|
1 Participants
|
Adverse Events
TAC-302
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TAC-302
n=52 participants at risk
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 participants at risk
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diverticulum intestinal haemorrhagic
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Reproductive system and breast disorders
Prostatitis
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
Other adverse events
| Measure |
TAC-302
n=52 participants at risk
TAC-302: TAC-302 200 mg administered orally twice per day after meals, for 12 weeks.
|
Placebo
n=24 participants at risk
Placebo: Placebo administered orally twice per day after meals, for 12 weeks.
|
|---|---|---|
|
Ear and labyrinth disorders
Deafness neurosensory
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Gastrointestinal disorders
Constipation
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
8.3%
2/24 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.8%
2/52 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Gastrointestinal disorders
Glossitis
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
General disorders
Pyrexia
|
3.8%
2/52 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Bacteriuria
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Bronchitis
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Cystitis
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Gastroenteritis
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Herpes virus infection
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Influenza
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Nasopharyngitis
|
3.8%
2/52 • Number of events 3 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Periodontitis
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Pharyngitis
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Pyuria
|
3.8%
2/52 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Urinary tract infection
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Vulvitis
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Enteritis infectious
|
3.8%
2/52 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Infections and infestations
Enterocolitis viral
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Injury, poisoning and procedural complications
Compression fracture
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Injury, poisoning and procedural complications
Fracture
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Injury, poisoning and procedural complications
Contusion
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Injury, poisoning and procedural complications
Post procedural haematuria
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Injury, poisoning and procedural complications
Tooth dislocation
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Investigations
Blood creatine phosphokinase increased
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
2/52 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Nervous system disorders
Headache
|
3.8%
2/52 • Number of events 2 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Renal and urinary disorders
Dysuria
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Renal and urinary disorders
Renal colic
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Renal and urinary disorders
Urethral pain
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Skin and subcutaneous tissue disorders
Miliaria
|
1.9%
1/52 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
0.00%
0/24 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/52 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
4.2%
1/24 • Number of events 1 • Baseline to Week 13 (12 weeks in treatment period and 1 week in Follow-up period)
All treated patients in the treatment period were used for the analysis. This analysis set includes patients enrolled in the treatment period who took the investigational drug at least once.
|
Additional Information
Taiho Pharmaceutical Co., Ltd.
Clinical Trial Registration Contact
Phone: +81-3-3293-2455
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place