Trial Outcomes & Findings for Efficacy and Safety Study to Evaluate Gadavist (Gadobutrol) as Contrast Agent in Magnetic Resonance Imaging (MRI) of Brain or Spine Diseases in Chinese Patients (NCT NCT00395460)

NCT ID: NCT00395460

Last Updated: 2015-06-08

Results Overview

CNR = (signal intensity \[SI\] lesion - SI normal tissue) / standard deviation (SD) background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

147 participants

Primary outcome timeframe

Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Results posted on

2015-06-08

Participant Flow

Participants were recruited at specialized study centers if they satisfied the inclusion and exclusion criteria. All had known or suspected central nervous system lesions (including cranial and spinal lesions) with an indication for contrast enhanced magnetic resonance imaging for diagnosis and further treatment.

Of 150 screened participants, 3 were not randomized (2 due to withdrawal of consent, and 1 due to poor physical condition). 147 participants were randomized to either Gadobutrol 0.1 mmol/kg body weight (BW) (72 participants) or Gadopentetate dimeglumine 0.1 mmol/kg BW (75 participants).

Participant milestones

Participant milestones
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Overall Study
STARTED
72
75
Overall Study
Received Treatment
71
75
Overall Study
COMPLETED
71
75
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Overall Study
Withdrawal by Subject
1
0

Baseline Characteristics

Efficacy and Safety Study to Evaluate Gadavist (Gadobutrol) as Contrast Agent in Magnetic Resonance Imaging (MRI) of Brain or Spine Diseases in Chinese Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=71 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=75 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Total
n=146 Participants
Total of all reporting groups
Age, Continuous
42.8 years
STANDARD_DEVIATION 12.24 • n=5 Participants
43.9 years
STANDARD_DEVIATION 10.1 • n=7 Participants
43.4 years
STANDARD_DEVIATION 11.17 • n=5 Participants
Sex: Female, Male
Female
33 Participants
n=5 Participants
42 Participants
n=7 Participants
75 Participants
n=5 Participants
Sex: Female, Male
Male
38 Participants
n=5 Participants
33 Participants
n=7 Participants
71 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Two participants in each treatment group had missing values for signal intensity for central nervous system lesions at pre- and post-contrast and could thus not be considered for evaluation.

CNR = (signal intensity \[SI\] lesion - SI normal tissue) / standard deviation (SD) background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background.

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=68 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=73 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast Magnetic Resonance Imaging (MRI) Scan of Central Nervous System (CNS) Lesions
50.41 Contrast to Noise ratio
Standard Deviation 38.448
43.47 Contrast to Noise ratio
Standard Deviation 39.178

SECONDARY outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases

The number of lesions in the magnetic resonance scans was recorded before and after injection of contrast agent for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=70 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=75 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan
Investigator
0.7 Lesions
Standard Deviation 2.56
0.1 Lesions
Standard Deviation 0.83
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan
Reader 2
1.4 Lesions
Standard Deviation 6.94
0.3 Lesions
Standard Deviation 1.87
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan
Reader 3
1.7 Lesions
Standard Deviation 9.72
0.3 Lesions
Standard Deviation 1.44
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan
Reader 4
0.5 Lesions
Standard Deviation 2.72
0.1 Lesions
Standard Deviation 0.93

SECONDARY outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases.

The change in diagnostic confidence was assessed based on post-contrast compared to pre-contrast scans as "improved", "unchanged" or "worsened" for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=70 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=75 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 4 - improved
60 Participants
63 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Investigator - improved
68 Participants
65 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Investigator - unchanged
2 Participants
10 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Investigator - worsened
0 Participants
0 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 2 - improved
55 Participants
61 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 2 - unchanged
15 Participants
14 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 2 - worsened
0 Participants
0 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 3 - improved
59 Participants
61 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 3 - unchanged
11 Participants
14 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 3 - worsened
0 Participants
0 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 4 - unchanged
8 Participants
12 Participants
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
Reader 4 - worsened
2 Participants
0 Participants

SECONDARY outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Lesion contrast enhancement of 1 participant in the Gadavist group was assessed by the investigator (but not the blinded readers) as 'not applicable'.

The degree of contrast enhancement was recorded on a 4-point scale as follows: 1 = No: lesion is not enhanced. 2 = Moderate: lesion is weakly enhanced. 3 = Good: lesion is clearly enhanced. 4 = Excellent: lesion is clearly and brightly enhanced. In case of more than one lesion, the lesion with maximum enhancement was to be assessed. The change in lesion contrast enhancement was assessed based on post-contrast in comparison to pre-contrast scans for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=70 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=75 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI
Investigator
2.4 Contrast enhancement score
Standard Deviation 0.87
2.2 Contrast enhancement score
Standard Deviation 0.87
Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI
Reader 2
2.1 Contrast enhancement score
Standard Deviation 1.21
2.0 Contrast enhancement score
Standard Deviation 1.22
Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI
Reader 3
1.7 Contrast enhancement score
Standard Deviation 0.98
1.6 Contrast enhancement score
Standard Deviation 0.89
Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI
Reader 4
2.2 Contrast enhancement score
Standard Deviation 1.05
2.1 Contrast enhancement score
Standard Deviation 1.09

SECONDARY outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Lesion contrast enhancement of 1 participant in the Gadavist group was assessed by the investigator (but not the blinded readers) as 'not applicable'.

Lesion delineation was recorded on a 4-point scale as follows: 1 = None: no or unclear delineation of the boundary between lesion and surrounding tissue; 2 = Moderate: some aspects of border delineation covered; 3 = Good: almost clear delineation, but not complete on relevant slices; 4 = Excellent: sharp and complete delineation. In case of more than one lesion, the lesion with maximum enhancement was assessed. Change in lesion delineation was assessed based on post-contrast in comparison to pre-contrast scans for investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=70 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=75 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions
Investigator
1.1 Lesion delineation score
Standard Deviation 0.73
1.0 Lesion delineation score
Standard Deviation 0.85
Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions
Reader 2
1.4 Lesion delineation score
Standard Deviation 0.89
1.3 Lesion delineation score
Standard Deviation 0.88
Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions
Reader 3
0.9 Lesion delineation score
Standard Deviation 0.71
0.8 Lesion delineation score
Standard Deviation 0.53
Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions
Reader 4
1.0 Lesion delineation score
Standard Deviation 0.81
0.9 Lesion delineation score
Standard Deviation 0.67

OTHER_PRE_SPECIFIED outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All valid case participants who received contrast injection. Subgroup: those with primary malignant brain tumor(s) / brain metastases. One participant in the Gadavist group had missing values for signal intensity for central nervous system lesions at pre- and post-contrast and could thus not be considered for evaluation.

CNR = (SI lesion - SI normal tissue) / SD background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background.

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=20 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=25 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases
54.95 Contrast to Noise ratio
Standard Deviation 42.405
46.56 Contrast to Noise ratio
Standard Deviation 30.074

OTHER_PRE_SPECIFIED outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All valid case participants who received contrast injection. Subgroup: those with CNS lesions other than primary malignant brain tumor(s) / brain metastases. 1 (Gadavist) and 2 participants (Magnevist) had missing values for signal intensity for CNS lesions pre- and post-contrast and could not be considered for evaluation.

CNR = (SI lesion - SI normal tissue) / SD background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background.

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=48 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=48 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases
48.51 Contrast to Noise ratio
Standard Deviation 36.985
41.86 Contrast to Noise ratio
Standard Deviation 43.379

OTHER_PRE_SPECIFIED outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Subgroup: participants with primary malignant brain tumor(s) / brain metastases

Investigators and blinded readers (reader 2, 3 and 4) were to record the number of lesions in the magnetic resonance scans before and after injection of contrast agent.

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=21 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=25 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases
Investigator
0.7 Lesions
Standard Deviation 2.61
0.4 Lesions
Standard Deviation 1.41
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases
Reader 2
0.4 Lesions
Standard Deviation 1.75
0.2 Lesions
Standard Deviation 0.55
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases
Reader 3
0.5 Lesions
Standard Deviation 2.18
0.2 Lesions
Standard Deviation 0.72
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases
Reader 4
0.1 Lesions
Standard Deviation 0.30
0.0 Lesions
Standard Deviation 0.20

OTHER_PRE_SPECIFIED outcome

Timeframe: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)

Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Subgroup: participants with CNS lesions other than primary malignant brain tumor(s) / brain metastases

Investigators and blinded readers (reader 2, 3 and 4= were to record the number of lesions in the magnetic resonance scans before and after injection of contrast agent.

Outcome measures

Outcome measures
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=49 Participants
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=50 Participants
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases
Investigator
0.7 Lesions
Standard Deviation 2.57
0 Lesions
Standard Deviation 0
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases
Reader 2
1.8 Lesions
Standard Deviation 8.20
0.3 Lesions
Standard Deviation 2.26
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases
Reader 3
2.2 Lesions
Standard Deviation 11.53
0.3 Lesions
Standard Deviation 1.70
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases
Reader 4
0.7 Lesions
Standard Deviation 3.24
0.2 Lesions
Standard Deviation 1.13

Adverse Events

Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875)
n=71 participants at risk
Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec)
GD 0.1 mmol/kg BW (Magnevist, BAY86-4882)
n=75 participants at risk
Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec
Gastrointestinal disorders
Nausea
1.4%
1/71 • Number of events 1
0.00%
0/75
Investigations
Alanine aminotransferase increased
1.4%
1/71 • Number of events 1
0.00%
0/75
Investigations
Aspartate aminotransferase increased
1.4%
1/71 • Number of events 1
0.00%
0/75
Metabolism and nutrition disorders
Hyponatraemia
0.00%
0/71
1.3%
1/75 • Number of events 1
Skin and subcutaneous tissue disorders
Erythema
0.00%
0/71
1.3%
1/75 • Number of events 1
General disorders
Feeling abnormal
0.00%
0/71
1.3%
1/75 • Number of events 1
Psychiatric disorders
Insomnia
1.4%
1/71 • Number of events 1
1.3%
1/75 • Number of events 1

Additional Information

Therapeutic Area Head

BAYER

Results disclosure agreements

  • Principal investigator is a sponsor employee PIs shall provide sponsor with an advance copy of any proposed publication or oral presentation at least ninety (90) days prior to the date of the planned submission or presentation. Sponsor shall have sixty (60) days to recommend any changes it reasonably believes are necessary for scientific purposes or to preserve the confidentiality of sponsor's confidential information. PIs agree that the adoption of such recommended changes shall not be unreasonably refused.
  • Publication restrictions are in place

Restriction type: OTHER