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This study will evaluate the safety and immunogenicity in healthy children and adolescents after one or two IM dose(s) of trivalent subunit inactivated flu vaccine.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TIV (3-8 years) | Experimental | Non-Naive subjects received one dose and naive subjects received two doses, administered 4 weeks apart, of investigational trivalent influenza vaccine (TIV) |
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| Control TIV (3-8 years) | Active Comparator | Non-Naive subjects received one dose and Naive subjects received two doses, administered 4 weeks apart, of control vaccine. Subjects aged 3 to <4 years and subjects aged 4 to 8 years received different control TIV. |
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| TIV ( 9-17 years) | Experimental | All subjects received one dose of investigational TIV. The subjects in this cohort were included only for safety analysis. |
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| Control TIV ( (9-17 years) | Active Comparator | All subjects received one dose of the control vaccine. The subjects from this cohort were included only for safety analysis. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TIV | Biological | Investigational egg-derived trivalent subunit influenza vaccine. |
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| Measure | Description | Time Frame |
|---|---|---|
| Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | The non-inferiority of the antibody responses of investigational TIV compared to control TIV assessed in terms of the percentage of subjects achieving seroconversion, against the three homologous vaccine strains,in children 3 to 8 years of age, at 21 days after last vaccination. Seroconversion was defined as a pre-vaccination haemagglutinin inhibition (HI) titer <1:10 and post-vaccination HI titer ≥1:40 or as a pre-vaccination HI titer ≥1:10 and at minimum four-fold rise in post-vaccination antibody titer | Day 22 for non-naive/Day 50 for naive subjects |
| Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | The non-inferiority of the antibody responses of investigational TIV compared to control vaccine assessed in terms of post vaccination GMTs, at 21 days after last vaccination against the three homologous vaccine strains in 3 to 8 year old children. | Day 22 for non-naive/Day 50 for naive subjects |
| Measure | Description | Time Frame |
|---|---|---|
| Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | The percentages of 3 to 8 year old subjects achieving HI titers ≥40 after receiving either one or two doses of investigational TIV or control vaccine, 21 days after last vaccination, are reported. This criterion according to the US (CBER)guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40, is ≥70%. |
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Inclusion Criteria:
Exclusion Criteria:
Parents or legal guardians and individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study
Parents or legal guardians and individuals providing assent who do not consent to the retention of the subject's serum samples after study completion
Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may have interfered with the subject's ability to participate in the study
Individuals with history or any illness that, in the opinion of the investigator, might have interfered with the results of the study or posed additional risk to the subjects due to participation in the study
History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to influenza viral proteins, latex, to any excipients, and to eggs (including ovalbumin), chicken protein, influenza viral protein, kanamycin, neomycin sulphate, cetyltrimethylammonium bromide (CTAB), polysorbate 80, neomycin, polymixin, formaldehyde, thimerosal, beta propiolactone, or nonoxynol-9
History of any serious disease, such as:
Known or suspected impairment/alteration of immune function, including:
Pregnant or breast-feeding female and any positive or indeterminate pregnancy test
Received an influenza vaccine within 6 months prior to Visit 1
Laboratory-confirmed or suspected influenza disease within 6 months prior to Visit 1
Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study
Experienced a fever and/or any acute illness within 3 days prior to each study vaccination
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centro de Atención e Investigación Medica - CAIMED | Carrera 42A # 17-50, Bogotá | Colombia | ||||
| Clinical research institute ,S.C(CRI), Blvd Manuel Avila Camacho 1994 Consultorio 1103 Col. San Lucas Tepetlacalco, C.P.54055 Tlalnepantla |
Due to GCP non-compliance at the Mexico site, data of 312 subjects (3-8 year olds) enrolled from this site were excluded from the final immunogenicity and safety analysis. The population was analyzed in the enrolled set.
The study was conducted in 13 centers across 4 countries: Mexico, Colombia, Panama and Philippines.
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| ID | Title | Description |
|---|---|---|
| FG000 | TIV (3-8 Years Old) | The group consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). The non-naive subjects received one dose and naive subjects received two doses of investigational TIV. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| TIVf | Biological | US licensed trivalent inactivated subunit influenza vaccine -Fluvirin (Novartis Vaccines and Diagnostics) is approved for use in subjects ≥4 years. |
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| Comparator TIV | Biological | US licensed trivalent subunit inactivated influenza vaccine- Fluzone (Sanofi Pasteur) is approved for use in children <4 years. |
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| Day 22 for non-naive/Day 50 for naive subjects |
| Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | The percentages of 3 to 8 years-old subjects achieving seroconversion in HI antibody titers after receiving either one or two doses of investigational TIV or control vaccine, at 21 days after last vaccination, are reported. This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 22 and day 50 (21 days after last vaccination) is ≥40. | Day 22 for non-naive/Day 50 for naive |
| Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | The percentage of 3 to 8 years-old vaccine-naive subjects achieving HI titers ≥40, after receiving two doses of investigational TIV or control vaccine. The time frame of evaluation was 28 days after first (Day 29) and 21 days after second vaccine dose (Day 50). This criterion according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%, for each vaccine strain. | Day 1, Day 29, and Day 50 |
| Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | The percentages of 3 to 8 years-old vaccine naive children achieving seroconversion or significant increase in HI antibody titers after receiving two doses of investigational TIV or control vaccine, are reported. The time frame of evaluation was 28 days after first (Day 29) and 21 days after the second dose (Day 50). This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 29 and day 50 is ≥40, for each vaccine strain. | Day 29 and Day 50 |
| Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | The number of 3-17 year old children with solicited local and systemic adverse events and other adverse events, after receiving either one or two doses of investigational TIV as compared to control vaccine are reported. | Day 1 to 7 after vaccination |
| Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | The number of 3-17 year old children reporting any unsolicited adverse event and any serious adverse event (SAE) after receiving either one or two doses of investigational TIV and control vaccine are reported. | Day 1 to 180 (non-naive )/Day 1 to 209 (naive) |
| Estado de México |
| Mexico |
| Centro de Salud Magally Ruiz, Street Bolivar | Panama - La Chorrera | Panama |
| Clinica Hospital San Fernando, Floor 4 Office 419 via España las Sabanas | Panama City | Panama |
| Consultorios America Floor 2 Office 201-1, Via España Vista Hermosa | Panama City | Panama |
| Consultorios Medicos San Judas Tadeo Principal Street, Floor 5 Office 507, Villa Lucre | Panama City | Panama |
| Philippine General Hospital | Taft Avenue, Manila | Manila | 1000 | Philippines |
| Research Institute for Tropical Medicine, Department of Health Compound | Filinvest Corporate City, Alabang | Muntinlupa City | 1781 | Philippines |
| Research Institute for Tropical Medicine, Department of Health Compound, FILINVEST Corporate City | Alabang, Muntinlupa City | 1781 | Philippines |
| University of the East Ramon Magsaysay Medical Center, 64 Aurora Boulevard | Barangay Dona Imelda Quezon City | 1113 | Philippines |
| De La Salle Health Sciences Institute | Dasmarinas Cavite | 4115 | Philippines |
| Mary Chiles General Hospital, 667 Gastambide St. Sampaloc | Manila | 1008 | Philippines |
| Philippine Children's Medical Center, Quezon Avenue corner Agham Road | Quezon City | Philippines |
| FG001 |
| Control (4-8 Years) |
The group consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). The non-naive subjects received one dose and naive subjects received two doses of US licensed control vaccine- TIVf. |
| FG002 | Control (3 to < 4 Years) | The group consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination.The non-naive subjects received one dose and naive subjects received two doses of US licensed control vaccine- comparator TIV. |
| FG003 | TIV (9-17 Years) | All subjects in this group were non-naive and received one dose of investigational TIV. |
| FG004 | Control (9-17 Years) | All subjects in this group were non-naive and received one dose of US licensed control vaccine TIVf. |
| COMPLETED |
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| NOT COMPLETED |
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Demography reported for all enrolled set except for 312 subjects (3-8 year olds) who were enrolled in the Mexico site.
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| ID | Title | Description |
|---|---|---|
| BG000 | TIV (3-8 Years) | The group consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). The non-naive subjects received one dose and naive subjects received two doses of investigational TIV. |
| BG001 | Control (3-8 Years) | The group [control (4-8 years) + control (3 to<4 years)] consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). Subjects (4-<9 years) received TIVf and subjects (3-<4 years) received comparator TIV. The non-naive subjects received one dose and naive subjects received two doses of vaccine. |
| BG002 | TIV (9-17 Years) | All subjects received one dose of investigational TIV. |
| BG003 | Control (9-17 Years) | All subjects received one dose of control TIV (eTIV_f). |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | The non-inferiority of the antibody responses of investigational TIV compared to control TIV assessed in terms of the percentage of subjects achieving seroconversion, against the three homologous vaccine strains,in children 3 to 8 years of age, at 21 days after last vaccination. Seroconversion was defined as a pre-vaccination haemagglutinin inhibition (HI) titer <1:10 and post-vaccination HI titer ≥1:40 or as a pre-vaccination HI titer ≥1:10 and at minimum four-fold rise in post-vaccination antibody titer | Analysis was done on per protocol population i.e-all subjects who correctly received study vaccinations,provided evaluable serum samples at the relevant time points, and had no major protocol violation as defined prior to unblinding. | Posted | Number | 95% Confidence Interval | Percentages | Day 22 for non-naive/Day 50 for naive subjects |
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| Secondary | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | The percentages of 3 to 8 year old subjects achieving HI titers ≥40 after receiving either one or two doses of investigational TIV or control vaccine, 21 days after last vaccination, are reported. This criterion according to the US (CBER)guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40, is ≥70%. | Analysis was performed on per protocol population. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Day 22 for non-naive/Day 50 for naive subjects |
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| Primary | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | The non-inferiority of the antibody responses of investigational TIV compared to control vaccine assessed in terms of post vaccination GMTs, at 21 days after last vaccination against the three homologous vaccine strains in 3 to 8 year old children. | Analysis was performed on the per protocol population. | Posted | Geometric Mean | 95% Confidence Interval | Titers | Day 22 for non-naive/Day 50 for naive subjects |
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| Secondary | Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | The percentages of 3 to 8 years-old subjects achieving seroconversion in HI antibody titers after receiving either one or two doses of investigational TIV or control vaccine, at 21 days after last vaccination, are reported. This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 22 and day 50 (21 days after last vaccination) is ≥40. | Analysis was performed on the per protocol population. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Day 22 for non-naive/Day 50 for naive |
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| Secondary | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | The percentage of 3 to 8 years-old vaccine-naive subjects achieving HI titers ≥40, after receiving two doses of investigational TIV or control vaccine. The time frame of evaluation was 28 days after first (Day 29) and 21 days after second vaccine dose (Day 50). This criterion according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%, for each vaccine strain. | Analysis was done on the per protocol population. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Day 1, Day 29, and Day 50 |
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| Secondary | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | The percentages of 3 to 8 years-old vaccine naive children achieving seroconversion or significant increase in HI antibody titers after receiving two doses of investigational TIV or control vaccine, are reported. The time frame of evaluation was 28 days after first (Day 29) and 21 days after the second dose (Day 50). This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 29 and day 50 is ≥40, for each vaccine strain. | Analysis was done on the per protocol population. | Posted | Number | 95% Confidence Interval | Percentages of subjects | Day 29 and Day 50 |
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| Secondary | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | The number of 3-17 year old children with solicited local and systemic adverse events and other adverse events, after receiving either one or two doses of investigational TIV as compared to control vaccine are reported. | Analysis was done on the safety set population i.e all subjects who received at least one study vaccine and provided post vaccination safety data. | Posted | Number | Subjects | Day 1 to 7 after vaccination |
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| Secondary | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | The number of 3-17 year old children reporting any unsolicited adverse event and any serious adverse event (SAE) after receiving either one or two doses of investigational TIV and control vaccine are reported. | Analysis was done on the safety set population. | Posted | Number | Subjects | Day 1 to 180 (non-naive )/Day 1 to 209 (naive) |
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Solicited adverse events collected from Day 1-7 after each vaccination. Serious adverse events and other unsolicited adverse events were collected from Day 1-180 for non-naive and Day 1-209 for vaccine-naive subjects.
The population analyzed here is the safety set.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TIV (3-8 Years) | The group consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). The non-naive subjects received one dose and naive subjects received two doses of investigational TIV. | 14 | 1,039 | 657 | 1,039 | ||
| EG001 | Control (3-8 Years) | The group [control (4-8 years) + control (3 to<4 years)] consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). Subjects (4-<9 years) received TIVf and subjects (3-<4 years) received comparator TIV. The non-naive subjects received one dose and naive subjects received two doses of control vaccine. | 3 | 531 | 342 | 531 | ||
| EG002 | TIV (9-17 Years) | All subjects received one dose of investigational TIV. | 4 | 817 | 385 | 817 | ||
| EG003 | Control (9-17 Years) | All subjects received one dose of control vaccine (TIV_f). | 3 | 412 | 196 | 412 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abscess | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Amoebiasis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Ascariasis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Bronchopneumonia | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Cholera | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Dengue fever | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Gastroenteritis bacterial | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Measles | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Injury | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Thermal burn | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Headache | Nervous system disorders | Non-systematic Assessment |
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| Suicide attempt | Psychiatric disorders | MedDRA | Non-systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| injection site pain | General disorders | Systematic Assessment |
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| malaise | General disorders | Systematic Assessment |
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| pyrexia | General disorders |
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| nasopharingitis | Infections and infestations |
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| upper respiratory tract infection | Infections and infestations |
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| fatigue | General disorders | Systematic Assessment |
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| myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| headache | Nervous system disorders | Systematic Assessment |
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| hyperhidrosis | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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Due to GCP non-compliance at the Mexico site, data of 312 subjects (3-8 year olds) enrolled from this site were excluded from the final immunogenicity and safety analysis.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Posting Director | Novartis Vaccines and Diagnostics | RegistryContactVaccinesUS@novartis.com |
| Male |
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| B strain |
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| Non-inferiority of investigational TIV to control TIV against A/H3N2 influenza strain | Vaccine group difference (%) | 10 | 2-Sided | 95 | 6 | 14 | Yes | Non-Inferiority or Equivalence | The investigational TIV was to be considered non-inferior to the control TIV if, for all three strains, the upper bound of the two-sided 95% CI on the difference between the seroconversion rates (Seroconversion control - Seroconversion investigational), at 21 days after last vaccination, does not exceed 10 percentage points |
| Non-inferiority of investigational TIV to the control TIV against B influenza strain | Vaccine group difference (%) | -1 | 2-Sided | 95 | -5 | 3 | Yes | Non-Inferiority or Equivalence | The investigational TIV was to be considered non-inferior to the control TIV if, for all three strains, the upper bound of the two-sided 95% CI on the difference between the seroconversion rates (Seroconversion control - Seroconversion investigational), at 21 days after last vaccination, does not exceed 10 percentage points |
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| Units | Counts |
|---|---|
| Participants |
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| OG002 | TIV (9-17 Years) | All subjects received one dose of investigational TIV. |
| OG003 | Control (9-17 Years) | All subjects received one dose of control vaccine(TIVf). |
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| TIV (9-17 Years) |
All subjects received one dose of investigational TIV. |
| OG003 | Control (9-17 Years) | All subjects received one dose of control vaccine (TIVf). |
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