A Maintenance Study With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01847274 |
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Recruitment Status :
Active, not recruiting
First Posted : May 6, 2013
Results First Posted : May 1, 2019
Last Update Posted : October 14, 2020
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Sponsor:
Tesaro, Inc.
Collaborators:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetics, Inc.
US Oncology Research
Sarah Cannon
Cooperative Ovarian Cancer Group (COGI)
Facing Our Risk of Cancer Empowered
Information provided by (Responsible Party):
Tesaro, Inc.
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Brief Summary:
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of niraparib as maintenance in platinum sensitive ovarian cancer patients who have either gBRCAmut or a tumor with high-grade serous histology and who have responded to their most recent chemotherapy containing a platinum agent. Niraparib is an orally active PARP inhibitor. Niraparib or placebo (in a 2:1 ratio) will be administered once daily continuously during a 28-day cycle. Health-related quality of life will be measured by the Functional Assessment of Cancer Therapy - Ovarian Symptom Index (FOSI), European Quality of Life scale, 5-Dimensions (EQ-5D), and a neuropathy questionnaire. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms (ECGs), and safety laboratory values.
The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in patients who have platinum sensitive ovarian cancer as assessed by the prolongation of progression free survival (PFS).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ovarian Neoplasms Platinum Sensitive Ovarian Cancer | Drug: Active comparator: Niraparib Drug: placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 578 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3 Randomized Double-blind Trial of Maintenance With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer. |
| Actual Study Start Date : | June 21, 2013 |
| Actual Primary Completion Date : | April 22, 2016 |
| Estimated Study Completion Date : | December 14, 2020 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Ovarian cancer
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Niraparib
2:1 Ratio administered once daily continuously during a 28 day cycle.
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Drug: Active comparator: Niraparib
Niraparib vs placebo 2:1 ratio
Other Name: Niraparib |
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Placebo Comparator: Placebo
Administered once daily continuously over a 28 day cycle.
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Drug: placebo |
Primary Outcome Measures :
- Progression-Free Survival (PFS) in Cohort With Germline BRCA Mutation (gBRCA) [ Time Frame: From date of randomization to the earliest date of disease progression or death from any cause. ]PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.
- Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+) [ Time Frame: From date of randomization to the earliest date of disease progression or death from any cause ]PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.
- Progression-Free Survival (PFS) in Cohort With No Germline BRCA Mutation (Non-gBRCA) [ Time Frame: From date of randomization to the earliest date of disease progression or death from any cause. ]PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion.
Secondary Outcome Measures :
- Time to First Subsequent Therapy (TFST) in Cohort With Germline BRCA Mutation (gBRCA) [ Time Frame: From date of randomization to the earliest date of first subsequent therapy or death. ]Patients were to be followed off treatment every 3 months for subsequent anti-cancer treatment. The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death.
- Time to First Subsequent Therapy (TFST) in Cohort With No Germline BRCA Mutation (Non-gBRCA) [ Time Frame: From date of randomization to the earliest date of first subsequent therapy or death. ]Patients were to be followed off treatment every 3 months for subsequent anti-cancer treatment. The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death.
- Chemotherapy-Free Interval (CFI) in Cohort With Germline BRCA Mutation (gBRCA) [ Time Frame: From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment. ]CFI was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment.
- Chemotherapy-Free Interval (CFI) in Cohort With No Germline BRCA Mutation (Non-gBRCA) [ Time Frame: From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment. ]CFI was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment.
- Progression-Free Survival 2 (PFS2) in Cohort With Germline BRCA Mutation (gBRCA) [ Time Frame: From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause. ]Patients were to be followed off treatment every 3 months for subsequent anti-cancer treatment, including outcome of such therapy, any new malignancies, and survival status. PFS2 was defined as the time from treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause. This study is ongoing, PFS2 is immature at this stage of primary analysis.
- Progression-Free Survival 2 (PFS2) in Cohort With No Germline BRCA Mutation (Non-gBRCA) [ Time Frame: From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause. ]Patients were to be followed off treatment every 3 months for subsequent anti-cancer treatment, including outcome of such therapy, any new malignancies, and survival status. PFS2 was defined as the time from treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause. This study is ongoing, PFS2 is immature at this stage of primary analysis.
- Overall Survival (OS) in Cohort With Germline BRCA Mutation (gBRCA) [ Time Frame: From treatment randomization to date of death by any cause ]Patients were to be followed off treatment every 3 months for survival status. Overall survival is defined as the date of randomization to the date of death by any cause. Results not yet reported.
- Overall Survival (OS) in Cohort With No Germline BRCA Mutation (Non-gBRCA) [ Time Frame: From treatment randomization to date of death by any cause ]Patients were to be followed off treatment every 3 months for survival status. Overall survival is defined as the date of randomization to the date of death by any cause. Results not yet reported.
- Time to Second Subsequent Therapy (TSST) in Cohort With Germline BRCA Mutation (gBRCA) [ Time Frame: From the date of randomization to the start date of the second subsequent anti-cancer therapy. ]Patients were to be followed off treatment every 3 months for subsequent anti-cancer treatment, including outcome of such therapy, any new malignancies, and survival status. TSST is defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death. Results not yet reported.
- Time to Second Subsequent Therapy (TSST) in Cohort With No Germline BRCA Mutation (Non-gBRCA) [ Time Frame: From the date of randomization to the start date of the second subsequent anti-cancer therapy. ]Patients were to be followed off treatment every 3 months for subsequent anti-cancer treatment, including outcome of such therapy, any new malignancies, and survival status. TSST is defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death. Results not yet reported.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With Germline BRCA [ Time Frame: At Cycle 2 ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With Germline BRCA [ Time Frame: At Cycle 4 ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With Germline BRCA [ Time Frame: At Cycle 6 ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With Germline BRCA [ Time Frame: At Post Progression ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With no Germline BRCA [ Time Frame: At Cycle 2 ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With no Germline BRCA [ Time Frame: At Cycle 4 ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With no Germline BRCA [ Time Frame: At Cycle 6 ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI) in Cohort With no Germline BRCA [ Time Frame: At Post Progression ]The FOSI is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Patients respond to their symptom experience over the past 7 days using a 5-point Likert scale. The total symptom index is calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA [ Time Frame: At Cycle 2 ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA [ Time Frame: At Cycle 4 ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA [ Time Frame: At Cycle 6 ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA [ Time Frame: At Post Progression ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA [ Time Frame: At Cycle 2 ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA [ Time Frame: At Cycle 4 ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA [ Time Frame: At Cycle 6 ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
- Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA [ Time Frame: At Post Progression ]EQ-5D-5L is a well-validated, general preference-based, health-related QoL instrument. The EQ-5D-5L encompasses 5 domains, asking patients to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Each domain is assigned a level, and levels are combined to create a 5-digit number describing the patient's health state. For each patient, an index value is determined from a published country-specific value set. This index value or utility score ranges from 0 to 1.00 (with 1.0 representing perfect health) and is used in the calculation of quality-adjusted life years (QALYs) that are used to inform economic valuations of health interventions. A positive change from baseline indicates improvement.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 18 years of age or older, female, any race
- Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer
- High grade (or grade 3) serous histology or known to have gBRCAmut
- Has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 6 month period between penultimate platinum regimen and progression of disease)
- Has responded to last the platinum regimen, remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
- ECOG 0-1
- Adequate bone marrow, kidney and liver function
Exclusion Criteria:
- Known hypersensitivity to the components of niraparib
- Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated)
- Symptomatic uncontrolled brain metastasis
- Is pregnant or breast feeding
- Immunocompromised patients
- Known active hepatic disease
- Prior treatment with a known PARP inhibitor
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01847274
Locations
Show 126 study locations
Sponsors and Collaborators
Tesaro, Inc.
European Network of Gynaecological Oncological Trial Groups (ENGOT)
Myriad Genetics, Inc.
US Oncology Research
Sarah Cannon
Cooperative Ovarian Cancer Group (COGI)
Facing Our Risk of Cancer Empowered
Investigators
| Study Director: | GSK Clinical Studies | GlaxoSmithKline |
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Tesaro, Inc. |
| ClinicalTrials.gov Identifier: | NCT01847274 |
| Other Study ID Numbers: |
213356 PR-30-5011-C ( Other Identifier: Tesaro ) |
| First Posted: | May 6, 2013 Key Record Dates |
| Results First Posted: | May 1, 2019 |
| Last Update Posted: | October 14, 2020 |
| Last Verified: | September 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
Keywords provided by Tesaro, Inc.:
|
ovarian cancer platinum sensitive gBRCAmut |
BRCA high-grade serous histology PARP inhibitor |
Additional relevant MeSH terms:
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Ovarian Neoplasms Carcinoma, Ovarian Epithelial Hypersensitivity Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases |
Gonadal Disorders Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Immune System Diseases Niraparib Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |