Trial Outcomes & Findings for Primary Vaccination Study With a Pneumococcal Conjugate Vaccine in Healthy Children 6 to 8 Weeks of Age (NCT NCT00533507)
NCT ID: NCT00533507
Last Updated: 2018-06-08
Results Overview
Concentrations are given as geometric mean concentrations (GMC) and expressed in Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter (EL.U/mL).
COMPLETED
PHASE3
230 participants
One month after the third dose
2018-06-08
Participant Flow
Participant milestones
| Measure |
Synflorix Group
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Overall Study
STARTED
|
230
|
|
Overall Study
COMPLETED
|
229
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Synflorix Group
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Primary Vaccination Study With a Pneumococcal Conjugate Vaccine in Healthy Children 6 to 8 Weeks of Age
Baseline characteristics by cohort
| Measure |
Synflorix Group
n=230 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Age, Continuous
|
6.4 weeks
STANDARD_DEVIATION 0.60 • n=5 Participants
|
|
Sex: Female, Male
Female
|
115 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
115 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Concentrations are given as geometric mean concentrations (GMC) and expressed in Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter (EL.U/mL).
Outcome measures
| Measure |
Synflorix Group
n=219 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Concentration of Anti-Protein D Antibodies
|
2277.6 EL.U/mL
Interval 2048.7 to 2532.1
|
PRIMARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Concentrations are given as geometric mean titers (GMC) and expressed in microgram per milliliter (µg/mL). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
Outcome measures
| Measure |
Synflorix Group
n=219 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-1
|
2.92 µg/mL
Interval 2.65 to 3.22
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-4
|
3.79 µg/mL
Interval 3.42 to 4.19
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-5
|
4.50 µg/mL
Interval 4.11 to 4.93
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-6B
|
1.69 µg/mL
Interval 1.47 to 1.94
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-7F
|
4.07 µg/mL
Interval 3.72 to 4.46
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-9V
|
3.90 µg/mL
Interval 3.51 to 4.32
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-14
|
5.69 µg/mL
Interval 5.1 to 6.35
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-18C
|
7.28 µg/mL
Interval 6.43 to 8.25
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-19F
|
8.04 µg/mL
Interval 7.37 to 8.78
|
|
Concentration of Anti-Pneumococcal Antibodies
Anti-23F
|
2.81 µg/mL
Interval 2.44 to 3.22
|
SECONDARY outcome
Timeframe: Before the first dose (pre) and one month after (post) the third dosePopulation: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, on subjects with available results
Anti-protein D antibody cut-off value assessed was greater than or equal to 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter (EL.U/mL).
Outcome measures
| Measure |
Synflorix Group
n=219 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Anti-Protein D Antibody Concentrations Above the Cut-Off Value
Pre (N=217)
|
38 subjects
|
|
Number of Subjects With Anti-Protein D Antibody Concentrations Above the Cut-Off Value
Post (N=219)
|
218 subjects
|
SECONDARY outcome
Timeframe: Before the first dose (pre) and one month after (post) the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-pneumococcal antibody cut-off value assessed was 0.05 microgram per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F.
Outcome measures
| Measure |
Synflorix Group
n=219 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-19F Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-23F Pre (N=219)
|
91 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-23F Post (N=219)
|
216 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-1 Pre (N=217)
|
111 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-1 Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-4 Pre (N=217)
|
85 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-4 Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-5 Pre (N=217)
|
149 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-5 Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-6B Pre (N=217)
|
107 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-6B Post (N=219)
|
215 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-7F Pre (N=218)
|
138 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-7F Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-9V Pre (N=218)
|
123 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-9V Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-14 Pre (N=218)
|
203 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-14 Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-18C Pre (N=219)
|
153 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-18C Post (N=219)
|
219 subjects
|
|
Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-19F Pre (N=219)
|
172 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-pneumococcal antibody cut-off value assessed was 0.05 microgram per milliliter (µg/mL).
Outcome measures
| Measure |
Synflorix Group
n=219 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Cross-Reactive Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-6A (N=219)
|
210 subjects
|
|
Number of Subjects With Cross-Reactive Pneumococcal Serotype Antibody Concentrations Above the Cut-Off Value
Anti-19A (N=218)
|
200 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Cut-off value for opsonophagocytic activity against pneumococcal antibody assessed was greater than or equal to 1:8 titer.
Outcome measures
| Measure |
Synflorix Group
n=103 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-1 (N=102)
|
98 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-4 (N=103)
|
103 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-5 (N=102)
|
101 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-6B (N=102)
|
89 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-7F (N=103)
|
103 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-9V (N=98)
|
98 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-14 (N=102)
|
101 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-18C (N=101)
|
99 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-19F (N=103)
|
101 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-Off Value
Opsono-23F (N=102)
|
98 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Cut-off value for opsonophagocytic activity against pneumococcal antibody assessed was greater than or equal to 1:8 titer.
Outcome measures
| Measure |
Synflorix Group
n=97 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Opsonophagocytic Activity Against Cross-Reactive Pneumococcal Serotypes Above the Cut-Off Value
Opsono-6A
|
87 subjects
|
|
Number of Subjects With Opsonophagocytic Activity Against Cross-Reactive Pneumococcal Serotypes Above the Cut-Off Value
Opsono-19A
|
38 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-polyribosyl-ribitol phosphate antibody cut-off value assessed was greater than or equal to 0.15 microgram per milliliter (μg/mL).
Outcome measures
| Measure |
Synflorix Group
n=58 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Anti-Polyribosyl-Ribitol Phosphate Antibody Concentrations Above the Cut-Off Value
|
58 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-diphteria and anti-tetanus toxoids antibody cut-off values assessed were greater than or equal to 0.10 International Units per milliliter (IU/mL).
Outcome measures
| Measure |
Synflorix Group
n=58 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Anti-Diphteria and Anti-Tetanus Toxoids Antibody Concentrations Above the Cut-Off Value
Anti-diphteria toxoid
|
58 subjects
|
|
Number of Subjects With Anti-Diphteria and Anti-Tetanus Toxoids Antibody Concentrations Above the Cut-Off Value
Anti-tetanus toxoid
|
58 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-PT, anti-FHA and anti-PRN cut-off values assessed were greater than or equal to 5 Enzyme-Linked Immuno Sorbent Assay (ELISA) units per milliliter (EL.U/mL).
Outcome measures
| Measure |
Synflorix Group
n=58 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Anti-Pertussis (PT), Anti-Filamentous Hemagglutinin (FHA) and Anti-Pertactin (PRN) Antibody Concentrations Above the Cut-Off Value
Anti-PT (N=58)
|
58 subjects
|
|
Number of Subjects With Anti-Pertussis (PT), Anti-Filamentous Hemagglutinin (FHA) and Anti-Pertactin (PRN) Antibody Concentrations Above the Cut-Off Value
Anti-FHA (N=58)
|
58 subjects
|
|
Number of Subjects With Anti-Pertussis (PT), Anti-Filamentous Hemagglutinin (FHA) and Anti-Pertactin (PRN) Antibody Concentrations Above the Cut-Off Value
Anti-PRN (N=57)
|
57 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-HBs antibody cut-off value assessed was greater than or equal to 10 milli-International Units per milliliter (mIU/mL).
Outcome measures
| Measure |
Synflorix Group
n=32 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Above the Cut-Off Value
|
32 subjects
|
SECONDARY outcome
Timeframe: One month after the third dosePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-poliovirus 1, 2 and 3 antibody cut-off value assessed was greater than or equal to 1:8 titer.
Outcome measures
| Measure |
Synflorix Group
n=44 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Anti-Poliovirus 1, 2 and 3 Antibody Titers Above the Cut-Off Value
Anti-poliovirus 1
|
44 subjects
|
|
Number of Subjects With Anti-Poliovirus 1, 2 and 3 Antibody Titers Above the Cut-Off Value
Anti-poliovirus 2
|
44 subjects
|
|
Number of Subjects With Anti-Poliovirus 1, 2 and 3 Antibody Titers Above the Cut-Off Value
Anti-poliovirus 3
|
44 subjects
|
SECONDARY outcome
Timeframe: Four months after the administration of the second dose of Rotarix™ vaccinePopulation: Analysis was performed on ATP cohort for analysis of immunogenicity, on subjects with available results
Anti-rotavirus IgA antibody cut-off value assessed was greater than or equal to 20 Units per milliliter (U/mL).
Outcome measures
| Measure |
Synflorix Group
n=51 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects With Anti-rotavirus Immunoglobulin A Antibody Concentrations Above the Cut-Off Value
|
44 subjects
|
SECONDARY outcome
Timeframe: During the 4-day (Day 0-3) period after each doseSolicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include diarrhoea, drowsiness, fever, irritability, loss of appetite, and vomiting
Outcome measures
| Measure |
Synflorix Group
n=230 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects Reporting Solicited Symptoms
Pain
|
146 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Redness
|
144 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Swelling
|
139 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Diarrhoea
|
7 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Drowsiness
|
190 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Fever
|
153 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Irritability
|
203 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Loss of appetite
|
159 subjects
|
|
Number of Subjects Reporting Solicited Symptoms
Vomiting
|
55 subjects
|
SECONDARY outcome
Timeframe: During the 31-day (Day 0-30) period after each doseAn AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
Outcome measures
| Measure |
Synflorix Group
n=230 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects Reporting Unsolicited Adverse Events (AE)
|
95 subjects
|
SECONDARY outcome
Timeframe: Up to one month after the third doseAn SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Outcome measures
| Measure |
Synflorix Group
n=230 Participants
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Number of Subjects Reporting Serious Adverse Events (SAE)
|
15 subjects
|
Adverse Events
Synflorix Group
Serious adverse events
| Measure |
Synflorix Group
n=230 participants at risk
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Infections and infestations
Urinary tract infection
|
2.6%
6/230
|
|
Infections and infestations
Bronchiolitis
|
1.7%
4/230
|
|
Infections and infestations
Gastroenteritis
|
0.87%
2/230
|
|
General disorders
Pyrexia
|
0.87%
2/230
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
0.43%
1/230
|
|
Infections and infestations
Bronchopneumonia
|
0.43%
1/230
|
|
Metabolism and nutrition disorders
Dehydration
|
0.43%
1/230
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.43%
1/230
|
|
Skin and subcutaneous tissue disorders
Dermatitis diaper
|
0.43%
1/230
|
|
Gastrointestinal disorders
Enterocolitis
|
0.43%
1/230
|
|
Infections and infestations
Gastroenteritis bacterial
|
0.43%
1/230
|
|
Infections and infestations
Kawasaki's disease
|
0.43%
1/230
|
|
Infections and infestations
Meningitis aseptic
|
0.43%
1/230
|
|
Infections and infestations
Upper respiratory tract infection
|
0.43%
1/230
|
|
Renal and urinary disorders
Vesicoureteric reflux
|
0.43%
1/230
|
Other adverse events
| Measure |
Synflorix Group
n=230 participants at risk
Subjects receiving Synflorix co-administered with Infanrix™ hexa at 1.5, 3 and 6 months of age, and co-administered with Rotarix™ at 1.5 and 3 months of age.
|
|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
23.5%
54/230
|
|
General disorders
Pain
|
63.5%
146/230
|
|
General disorders
Redness
|
62.6%
144/230
|
|
General disorders
Swelling
|
60.4%
139/230
|
|
General disorders
Drowsiness
|
82.6%
190/230
|
|
General disorders
Fever
|
66.5%
153/230
|
|
General disorders
Irritability
|
88.3%
203/230
|
|
General disorders
Loss of appetite
|
69.1%
159/230
|
|
General disorders
Vomiting
|
23.9%
55/230
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER