Trial Outcomes & Findings for Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis (NCT NCT00764309)
NCT ID: NCT00764309
Last Updated: 2012-02-29
Results Overview
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
47 participants
Primary outcome timeframe
From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 years
Results posted on
2012-02-29
Participant Flow
Of the 47 participants enrolled, 31 were treated. Reasons for not entering treatment period were: withdrew consent-1, lost to follow up-2, no longer met study criteria-12, other reasons-1.
Participant milestones
| Measure |
100 mg Dasatinib, Oral Administration
Participants received 100 mg dasatinib once daily orally for up to 2 years (6 months of dosing to evaluate the primary endpoint + 18 months of dosing to assess longer-term safety and efficacy)
|
|---|---|
|
Overall Study
STARTED
|
31
|
|
Overall Study
COMPLETED
|
31
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety Evaluation of Dasatinib in Subjects With Scleroderma Pulmonary Fibrosis
Baseline characteristics by cohort
| Measure |
100 mg Dasatinib, Oral Administration
n=31 Participants
Participants received 100 mg dasatinib once daily orally for up to 2 years (6 months of dosing to evaluate the primary endpoint + 18 months of dosing to assess longer-term safety and efficacy)
|
|---|---|
|
Age Continuous
|
50.8 years
STANDARD_DEVIATION 12.44 • n=5 Participants
|
|
Age, Customized
<65 years
|
26 Years
n=5 Participants
|
|
Age, Customized
>=65 years
|
5 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
24 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black / African American
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian/Alaska Native
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic/Latino
|
3 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic/Latino
|
28 participants
n=5 Participants
|
|
Baseline Pulmonary Function: Diffusion capacity
|
14.223 mL/min/mmHg
STANDARD_DEVIATION 4.8012 • n=5 Participants
|
|
Baseline Pulmonary Function
FVC, n=30
|
2.955 Liters
STANDARD_DEVIATION 0.7978 • n=5 Participants
|
|
Baseline Pulmonary Function
FEV1, n=30
|
2.614 Liters
STANDARD_DEVIATION 1.3495 • n=5 Participants
|
|
Baseline Pulmonary Function
TLC, n=26
|
4.292 Liters
STANDARD_DEVIATION 1.1784 • n=5 Participants
|
|
Time from Initial Scleroderma Diagnosis to Start of Study
< 12 months
|
12 Participants
n=5 Participants
|
|
Time from Initial Scleroderma Diagnosis to Start of Study
12 - 23 months
|
8 Participants
n=5 Participants
|
|
Time from Initial Scleroderma Diagnosis to Start of Study
24 - 36 months
|
7 Participants
n=5 Participants
|
|
Time from Initial Scleroderma Diagnosis to Start of Study
> 36 months
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 yearsPopulation: All treated participants.
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.
Outcome measures
| Measure |
100 mg Dasatinib, Oral Administration
n=31 Participants
Participants received 100 mg dasatinib once daily orally for up to 2 years (6 months of dosing to evaluate the primary endpoint + 18 months of dosing to assess longer-term safety and efficacy)
|
|---|---|
|
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
Deaths
|
0 Participants
|
|
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
AEs
|
31 Participants
|
|
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
SAEs
|
7 Participants
|
|
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
Drug-Related Death
|
0 Participants
|
|
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
Drug-Related AEs
|
24 Participants
|
|
Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), or Adverse Events (AEs)
Drug-Related SAEs
|
5 Participants
|
PRIMARY outcome
Timeframe: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 yearsPopulation: All treated participants.
Participants who discontinued the study due to any AEs were recorded. Significant drug-related discontinuations were those SAEs recorded on the SAE case report forms with relationship to study drug of related or missing and action taken regarding study drug of discontinued or missing.
Outcome measures
| Measure |
100 mg Dasatinib, Oral Administration
n=31 Participants
Participants received 100 mg dasatinib once daily orally for up to 2 years (6 months of dosing to evaluate the primary endpoint + 18 months of dosing to assess longer-term safety and efficacy)
|
|---|---|
|
Reasons for Discontinuation of Study Treatment
Unforeseen toxicity of dasatinib
|
0 Participants
|
|
Reasons for Discontinuation of Study Treatment
AEs
|
13 Participants
|
|
Reasons for Discontinuation of Study Treatment
SAEs
|
4 Participants
|
|
Reasons for Discontinuation of Study Treatment
Drug-Related AEs
|
8 Participants
|
|
Reasons for Discontinuation of Study Treatment
Drug-Related SAEs
|
3 Participants
|
|
Reasons for Discontinuation of Study Treatment
Significant Drug-Related Pericardial Effusion
|
0 Participants
|
|
Reasons for Discontinuation of Study Treatment
Significant Drug-Related Pleural Effusion
|
2 Participants
|
|
Reasons for Discontinuation of Study Treatment
Significant Drug-Related Bone Marrow Suppression
|
0 Participants
|
|
Reasons for Discontinuation of Study Treatment
Significant Worsening of Underlying Scleroderma
|
0 Participants
|
|
Reasons for Discontinuation of Study Treatment
Significant Drug-Related Peripheral Edema
|
0 Participants
|
PRIMARY outcome
Timeframe: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 yearsPopulation: All treated participants.
Toxicity was graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0. (Grade (GR)0=normal, GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening). Granulocyte count (x 10\^9 /L), GR1: ≥1.0 - \<1.5, GR2: ≥0.5 - \<1.0; Hemoglobin (g/dL), GR0: 13-17, GR1: \<13 - 10.0 , GR2: 8.0 - \<10.0, GR3: 6.5 - \<8.0; Platelet count (x 10\^9 /L) GR0: 150-400, GR2: ≥50.0 - \<75.0; Leukocyte count (x 10\^9 /L ), GR0: 3.5-11.1, GR2: 2.0 - \<3.0.
Outcome measures
| Measure |
100 mg Dasatinib, Oral Administration
n=31 Participants
Participants received 100 mg dasatinib once daily orally for up to 2 years (6 months of dosing to evaluate the primary endpoint + 18 months of dosing to assess longer-term safety and efficacy)
|
|---|---|
|
Laboratory Test Results Summary of Toxicity: Hematology
Granulocyte count, GR0
|
28 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Granulocyte count, GR1
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Granulocyte count, GR2
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Granulocyte count, GR not reported
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Hemoglobin, GR0
|
4 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Hemoglobin, GR1
|
17 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Hemoglobin, GR2
|
8 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Hemoglobin, GR3
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Hemoglobin, GR not reported
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Platelet count, GR0
|
29 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Platelet count, GR2
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Platelet count, GR not reported
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Leukocyte count, GR0
|
29 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Leukocyte count, GR2
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Hematology
Leukocyte count, GR not reported
|
1 participants
|
PRIMARY outcome
Timeframe: From start of study drug therapy up to 30 days after the last dose. The duration of dasatinib dosing in this study was up to 2 yearsPopulation: All treated participants.
GR0=normal,1=mild,2=moderate,3=severe,4=life-threatening. ALP(U/L) GR0:40-135,GR1:\>135-337; ALT(U/L) GR0:0-47,GR1:\>47-117; AST(U/L) GR0:0-37,GR1:\>37-93; High(↑) Calcium(mg/dL) GR0:8.4-10.2,GR1:\>10.2-11.5; Low(↓) Calcium(mg/dL) GR0:8.4-10.2,GR1:\<8.4-8.0,GR2:7.0-\<8.0; CK(U/L) GR0:24-195,GR1:\>195-488, GR2:\>488-975; Creatinine(mg/dL) GR0:0.6-1.4,GR1:\>1.4-2.1,GR2:\>2.1-4.2; ↑Potassium(mEq/L) GR0:3.6-5.2,GR1:\>5.2-5.5,GR2:\>5.5-6.0; ↑Sodium(mEq/L) GR0:134-146; ↓Sodium(mEq/L) GR0:134-146,GR1:\<134-130; Inorganic Phosphorus(mg/dL) GR0:2.4-4.9,GR2:≥2.0-\<2.5; Total Bilirubin(mg/dL) GR0:0-1.1,GR1:\>1.1-2.75.
Outcome measures
| Measure |
100 mg Dasatinib, Oral Administration
n=31 Participants
Participants received 100 mg dasatinib once daily orally for up to 2 years (6 months of dosing to evaluate the primary endpoint + 18 months of dosing to assess longer-term safety and efficacy)
|
|---|---|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Alkaline Phosphatase (ALP), GR0
|
30 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
ALP, GR1
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Alanine Aminotransferase (ALT), GR0
|
24 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
ALT, GR1
|
7 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Aspartate Aminotransferase (AST), GR0
|
21 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
AST, GR1
|
10 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
High Calcium, GR0
|
23 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
High Calcium, GR1
|
8 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Low Calcium, GR0
|
28 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Low Calcium, GR1
|
2 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Low Calcium, GR2
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Creatine Kinase (CK), GR0
|
16 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
CK, GR1
|
11 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
CK, GR2
|
2 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
CK, GR not reported
|
2 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Creatinine, GR 0
|
26 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Creatinine, GR1
|
3 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Creatinine, GR2
|
2 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
High Potassium, GR0
|
28 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
High Potassium, GR1
|
2 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
High Potassium, GR2
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Low Potassium, GR 0
|
27 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Low Potassium, GR 1
|
4 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
High Sodium, GR0
|
31 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Low Sodium, GR0
|
28 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Low Sodium, GR1
|
3 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Inorganic Phosphorus, GR 0
|
30 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Inorganic Phosphorus, GR 2
|
1 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Total Bilirubin, GR0
|
30 participants
|
|
Laboratory Test Results Summary of Toxicity: Blood Chemistry Per (NCI-CTCAE) Version 3.0 Grade (GR)
Total Bilirubin, GR1
|
1 participants
|
Adverse Events
Dasatinib
Serious events: 7 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dasatinib
n=31 participants at risk
|
|---|---|
|
Cardiac disorders
ATRIAL FLUTTER
|
3.2%
1/31
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
3.2%
1/31
|
|
Cardiac disorders
DIASTOLIC DYSFUNCTION
|
3.2%
1/31
|
|
Gastrointestinal disorders
HAEMATEMESIS
|
3.2%
1/31
|
|
General disorders
FACE OEDEMA
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
3.2%
1/31
|
|
Infections and infestations
CYSTITIS
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
FLUID OVERLOAD
|
3.2%
1/31
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
3.2%
1/31
|
|
Infections and infestations
CLOSTRIDIAL INFECTION
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
3.2%
1/31
|
Other adverse events
| Measure |
Dasatinib
n=31 participants at risk
|
|---|---|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
16.1%
5/31
|
|
Gastrointestinal disorders
DYSPEPSIA
|
6.5%
2/31
|
|
Gastrointestinal disorders
NAUSEA
|
25.8%
8/31
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
9.7%
3/31
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
12.9%
4/31
|
|
Gastrointestinal disorders
CONSTIPATION
|
25.8%
8/31
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
6.5%
2/31
|
|
Blood and lymphatic system disorders
LYMPHADENOPATHY
|
9.7%
3/31
|
|
Gastrointestinal disorders
PARAESTHESIA ORAL
|
6.5%
2/31
|
|
Investigations
WEIGHT DECREASED
|
9.7%
3/31
|
|
Reproductive system and breast disorders
ERECTILE DYSFUNCTION
|
6.5%
2/31
|
|
Vascular disorders
FLUSHING
|
6.5%
2/31
|
|
Investigations
HAEMOGLOBIN DECREASED
|
9.7%
3/31
|
|
Psychiatric disorders
INSOMNIA
|
16.1%
5/31
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL STIFFNESS
|
9.7%
3/31
|
|
Infections and infestations
URINARY TRACT INFECTION
|
12.9%
4/31
|
|
Investigations
CARBON MONOXIDE DIFFUSING CAPACITY DECREASED
|
6.5%
2/31
|
|
Gastrointestinal disorders
DIARRHOEA
|
38.7%
12/31
|
|
Nervous system disorders
DIZZINESS
|
12.9%
4/31
|
|
Gastrointestinal disorders
GLOSSODYNIA
|
6.5%
2/31
|
|
Gastrointestinal disorders
HAEMATOCHEZIA
|
6.5%
2/31
|
|
Musculoskeletal and connective tissue disorders
LIMB DISCOMFORT
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
SKIN TIGHTNESS
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
9.7%
3/31
|
|
Infections and infestations
BRONCHITIS
|
6.5%
2/31
|
|
General disorders
CHEST PAIN
|
6.5%
2/31
|
|
Infections and infestations
INFECTED SKIN ULCER
|
6.5%
2/31
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
9.7%
3/31
|
|
Gastrointestinal disorders
RECTAL HAEMORRHAGE
|
6.5%
2/31
|
|
General disorders
FATIGUE
|
38.7%
12/31
|
|
Infections and infestations
FOLLICULITIS
|
6.5%
2/31
|
|
Gastrointestinal disorders
GASTROOESOPHAGEAL REFLUX DISEASE
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
6.5%
2/31
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
12.9%
4/31
|
|
General disorders
PYREXIA
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
RASH
|
19.4%
6/31
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
25.8%
8/31
|
|
Nervous system disorders
HEADACHE
|
25.8%
8/31
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HYPERTENSION
|
6.5%
2/31
|
|
Infections and infestations
SINUSITIS
|
12.9%
4/31
|
|
Investigations
VITAL CAPACITY DECREASED
|
6.5%
2/31
|
|
Blood and lymphatic system disorders
ANAEMIA
|
19.4%
6/31
|
|
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
|
9.7%
3/31
|
|
Psychiatric disorders
DEPRESSION
|
12.9%
4/31
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
12.9%
4/31
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
6.5%
2/31
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL DISCOMFORT
|
9.7%
3/31
|
|
General disorders
OEDEMA PERIPHERAL
|
19.4%
6/31
|
|
Cardiac disorders
PALPITATIONS
|
6.5%
2/31
|
|
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
|
9.7%
3/31
|
|
Vascular disorders
RAYNAUD'S PHENOMENON
|
9.7%
3/31
|
|
Respiratory, thoracic and mediastinal disorders
SINUS CONGESTION
|
6.5%
2/31
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
12.9%
4/31
|
|
Gastrointestinal disorders
VOMITING
|
25.8%
8/31
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication
- Publication restrictions are in place
Restriction type: OTHER