TOPACIO: Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer
Study Details
Study Description
Brief Summary
This Phase 1/2 study will evaluate the safety and efficacy of combination treatment with niraparib and pembrolizumab (MK-3475) in patients with advanced or metastatic triple-negative breast cancer or recurrent ovarian cancer. (KEYNOTE-162)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: niraparib plus pembrolizumab Phase 1: Dose-escalation: ascending doses of niraparib up to 300mg/day orally (PO) on Days 1-21 and pembrolizumab 200mg intravenously (IV) on Day 1 of each 21-day cycle Phase 2: niraparib (recommended Phase 2 dose) in combination with pembrolizumab 200mg IV on Day 1 of each 21-day cycle |
Drug: niraparib
Biological: pembrolizumab
|
Outcome Measures
Primary Outcome Measures
- Phase 1: Number of Subjects Reporting Dose-Limiting Toxicities (DLTs) [During Cycle 1, ie, during the first 21 days of treatment]
DLTs are defined as: Any treatment-related Grade ≥ 3 non-hematologic clinical (non-laboratory) AE Any treatment-related Grade 3 or Grade 4 non-hematologic lab abnormality if: - Medical intervention is required to treat the patient, or - The abnormality leads to hospitalization, or - The abnormality persists for ≥ 7 days. Any treatment-related hematologic toxicity specifically defined as: - Thrombocytopenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with bleeding or requiring platelet transfusion; - Neutropenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with infection or febrile neutropenia; - Anemia Grade 4, or Grade 3 or 4 requiring blood transfusion. Any treatment-related AE leading to niraparib dose interruption per the following criteria: - A dose interruption for a non-DLT lab abnormality lasting ≥ 14 days. - A dose in interruption per dose modification rules for nonhematologic AE leading to < 80% of an intended dose being administered.
- Phase 2: Objective Response Rate (ORR) [Up to 40 weeks]
ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Secondary Outcome Measures
- To Evaluate the Safety and Tolerability of Combination Treatment With Niraparib and Pembrolizumab Using Common Terminology Criteria for Adverse Events (CTCAE, v4.03) [AEs were collected up to 90 days following the last dose of study treatment, where the median duration of treatment was 3 months.]
Percentage of patients with at least 1 Treatment-Emergent Adverse Event. Refer to the adverse event tables for specific details.
- Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST) [Radiographic evaluations were conducted every 9 weeks while on study treatment (every 12 weeks after 1 year of scans) independent of cycle delays and/or dose interruptions, and/or at any time when progression of disease is suspected.]
ORR by irRECIST is defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) using immune-related RECIST criteria.
- Phase 2: Duration of Response (DOR) [From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the Investigator until time of first documented progression.]
From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the investigator until time of first documented progression or death by any cause. No maximum timeframe was specified in the protocol.
- Phase 2: Disease Control Rate (DCR) [Up to 40 weeks]
DCR is defined as the percentage of patients who achieved a CR or PR or stable disease (SD) using RECIST (v1.1) as assessed by the Investigator.
- Phase 2: Progression Free Survival (PFS) [From date of first dose to the earlier date of assessment of progression of death by any cause in the absence of progression.]
From date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression. No maximum timeframe was specified in the protocol.
- Phase 2: Overall Survival (OS) [From date of first dose to the date of death by any cause.]
Patients were followed off treatment every 90 days for survival status. Overall survival is defined as the time from first dose to the date of death by any cause. No maximum timeframe was specified in the protocol.
- Phase 1 and Phase 2: To Evaluate the Pharmacokinetics (PK) of Niraparib and Associated Major Metabolite M1 During Combination Treatment. [Approximately 9 months]
Area Under the Curve (AUC), Minimum Concentration (Cmin), Maximum Concentration (Cmax), Clearance After Oral Administration (CL/F), Volume of Distribution After Oral Administration (Vz/F), AUC at Steady State (AUCss), Cmin at Steady State (Cmin,ss), Cmax at Steady State (Cmax,ss).
Eligibility Criteria
Criteria
Main Inclusion Criteria:
- Patient has histologically proven advanced (unresectable) or metastatic cancer as outlined below according to study phase and disease type:
- Phase 1 patients (breast or ovarian cancer)
-
Patients with advanced or metastatic breast cancer must have disease that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative (ie, TNBC). Patients with advanced or metastatic disease may have up to 4 lines of cytotoxic therapy. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy.
-
Patients must have any epithelial (ie, serous, endometroid, mucinous, clear cell) ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have received up to 5 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant and adjuvant therapies are not counted towards lines of therapy.
- Phase 2 patients (breast or ovarian cancer)
-
Patients with advanced or metastatic breast cancer must have TNBC. Patients with advanced or metastatic disease may have received up to 2 lines of cytotoxic therapy. Adjuvant and/or neoadjuvant therapies are not counted in the number of lines of therapy. TNBC patients who have previously received platinum chemotherapy in the metastatic setting are allowed to enroll in the study as long as they did not progress while on or within 8 weeks from the day of the last platinum administration.
-
Patients must have with high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer. Patients must have experienced a response lasting at least 6 months to first-line platinum-based therapy but currently considered to have platinum-resistant disease per investigator's assessment (e.g, patient is not eligible for further platinum containing treatment). Patients may have had up to 4 lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant, adjuvant, and the combination of both will be considered as one line of therapy.
-
Archival tumor tissue available or a fresh biopsy must be obtained prior to study treatment initiation
-
Measurable lesions by RECIST v1.1
-
Eastern Cooperative Oncology Group (ECOG) 0 or 1
-
Adequate organ function
-
Able to take oral medications
-
Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours of taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment
-
Male patient agrees to use an adequate method of contraception
Main Exclusion Criteria:
-
Patients with primary platinum refractory ovarian cancer (ie, progressive disease on or within 6 months of first-line platinum therapy)
-
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis Note: Patients previously treated for brain metastases may be able to participate provided they are stable
-
Patient has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
-
Poor medical risk
-
Condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
-
Pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study
-
Immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
-
Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
-
Known active hepatitis B or hepatitis C
-
Active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
-
Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
-
Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor
-
Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening
-
Known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Birmingham | Alabama | United States | 35249 |
| 2 | GSK Investigational Site | Phoenix | Arizona | United States | 85054 |
| 3 | GSK Investigational Site | Scottsdale | Arizona | United States | 85258 |
| 4 | GSK Investigational Site | Los Angeles | California | United States | 90048 |
| 5 | GSK Investigational Site | San Francisco | California | United States | 94115 |
| 6 | GSK Investigational Site | Stanford | California | United States | 94305 |
| 7 | GSK Investigational Site | Washington | District of Columbia | United States | 20007 |
| 8 | GSK Investigational Site | Deerfield Beach | Florida | United States | 33442 |
| 9 | GSK Investigational Site | Jacksonville | Florida | United States | 32224 |
| 10 | GSK Investigational Site | Miami | Florida | United States | 33136 |
| 11 | GSK Investigational Site | Orlando | Florida | United States | 32804 |
| 12 | GSK Investigational Site | Chicago | Illinois | United States | 60637 |
| 13 | GSK Investigational Site | Covington | Louisiana | United States | 70433 |
| 14 | GSK Investigational Site | Boston | Massachusetts | United States | 02111 |
| 15 | GSK Investigational Site | Boston | Massachusetts | United States | 02114 |
| 16 | GSK Investigational Site | Boston | Massachusetts | United States | 02115 |
| 17 | GSK Investigational Site | Burlington | Massachusetts | United States | 01805 |
| 18 | GSK Investigational Site | Detroit | Michigan | United States | 48201 |
| 19 | GSK Investigational Site | Rochester | Minnesota | United States | 55905 |
| 20 | GSK Investigational Site | Morristown | New Jersey | United States | 07962 |
| 21 | GSK Investigational Site | New York | New York | United States | 10065 |
| 22 | GSK Investigational Site | Chapel Hill | North Carolina | United States | 27514 |
| 23 | GSK Investigational Site | Charlotte | North Carolina | United States | 28204 |
| 24 | GSK Investigational Site | Cleveland | Ohio | United States | 44106 |
| 25 | GSK Investigational Site | Oklahoma City | Oklahoma | United States | 73104 |
| 26 | GSK Investigational Site | Germantown | Tennessee | United States | 38138 |
| 27 | GSK Investigational Site | Nashville | Tennessee | United States | 37203 |
| 28 | GSK Investigational Site | San Antonio | Texas | United States | 78229 |
| 29 | GSK Investigational Site | Charlottesville | Virginia | United States | 22903 |
| 30 | GSK Investigational Site | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Tesaro, Inc.
- Merck Sharp & Dohme LLC
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
More Information
Publications
None provided.- 213363
- 3000-PN162-01-001
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab |
|---|---|---|---|---|
| Arm/Group Description | Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Niraparib 300 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Ovarian Cancer: Niraparib 200mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Triple Negative Breast Cancer: Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. |
| Period Title: Overall Study | ||||
| STARTED | 7 | 7 | 53 | 55 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 7 | 7 | 53 | 55 |
Baseline Characteristics
| Arm/Group Title | Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Niraparib 300 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Ovarian Cancer: Niraparib 200mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Triple Negative Breast Cancer: Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Total of all reporting groups |
| Overall Participants | 7 | 7 | 53 | 55 | 122 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
4
57.1%
|
4
57.1%
|
37
69.8%
|
47
85.5%
|
92
75.4%
|
| >=65 years |
3
42.9%
|
3
42.9%
|
16
30.2%
|
8
14.5%
|
30
24.6%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
7
100%
|
7
100%
|
53
100%
|
55
100%
|
122
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
1
14.3%
|
0
0%
|
3
5.7%
|
3
5.5%
|
7
5.7%
|
| Not Hispanic or Latino |
6
85.7%
|
6
85.7%
|
50
94.3%
|
51
92.7%
|
113
92.6%
|
| Unknown or Not Reported |
0
0%
|
1
14.3%
|
0
0%
|
1
1.8%
|
2
1.6%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
3
5.7%
|
2
3.6%
|
5
4.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
1
1.9%
|
8
14.5%
|
9
7.4%
|
| White |
7
100%
|
7
100%
|
46
86.8%
|
43
78.2%
|
103
84.4%
|
| More than one race |
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
3
5.7%
|
2
3.6%
|
5
4.1%
|
| Region of Enrollment (Count of Participants) | |||||
| United States |
7
100%
|
7
100%
|
53
100%
|
55
100%
|
122
100%
|
Outcome Measures
| Title | Phase 1: Number of Subjects Reporting Dose-Limiting Toxicities (DLTs) |
|---|---|
| Description | DLTs are defined as: Any treatment-related Grade ≥ 3 non-hematologic clinical (non-laboratory) AE Any treatment-related Grade 3 or Grade 4 non-hematologic lab abnormality if: - Medical intervention is required to treat the patient, or - The abnormality leads to hospitalization, or - The abnormality persists for ≥ 7 days. Any treatment-related hematologic toxicity specifically defined as: - Thrombocytopenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with bleeding or requiring platelet transfusion; - Neutropenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with infection or febrile neutropenia; - Anemia Grade 4, or Grade 3 or 4 requiring blood transfusion. Any treatment-related AE leading to niraparib dose interruption per the following criteria: - A dose interruption for a non-DLT lab abnormality lasting ≥ 14 days. - A dose in interruption per dose modification rules for nonhematologic AE leading to < 80% of an intended dose being administered. |
| Time Frame | During Cycle 1, ie, during the first 21 days of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The assessment of DLTs in Phase 1 included only those patients completing the first cycle of therapy, unless the patient discontinued study drug due to a DLT. |
| Arm/Group Title | Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab |
|---|---|---|
| Arm/Group Description | Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Niraparib 300 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. |
| Measure Participants | 6 | 6 |
| Count of Participants [Participants] |
1
14.3%
|
1
14.3%
|
| Title | Phase 2: Objective Response Rate (ORR) |
|---|---|
| Description | ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Time Frame | Up to 40 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on all patients who received at least one dose of study medication. |
| Arm/Group Title | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab |
|---|---|---|
| Arm/Group Description | Ovarian Cancer: Niraparib 200mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Triple Negative Breast Cancer: Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. |
| Measure Participants | 53 | 55 |
| Number (90% Confidence Interval) [percentage of participants] |
15.1
215.7%
|
18.2
260%
|
| Title | To Evaluate the Safety and Tolerability of Combination Treatment With Niraparib and Pembrolizumab Using Common Terminology Criteria for Adverse Events (CTCAE, v4.03) |
|---|---|
| Description | Percentage of patients with at least 1 Treatment-Emergent Adverse Event. Refer to the adverse event tables for specific details. |
| Time Frame | AEs were collected up to 90 days following the last dose of study treatment, where the median duration of treatment was 3 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on all patients who received at least one dose of study medication. |
| Arm/Group Title | Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab |
|---|---|---|---|---|
| Arm/Group Description | Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Niraparib 300 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Ovarian Cancer: Niraparib 200mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Triple Negative Breast Cancer: Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. |
| Measure Participants | 7 | 7 | 53 | 55 |
| Count of Participants [Participants] |
7
100%
|
7
100%
|
53
100%
|
55
100%
|
| Title | Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST) |
|---|---|
| Description | ORR by irRECIST is defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) using immune-related RECIST criteria. |
| Time Frame | Radiographic evaluations were conducted every 9 weeks while on study treatment (every 12 weeks after 1 year of scans) independent of cycle delays and/or dose interruptions, and/or at any time when progression of disease is suspected. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected. |
| Arm/Group Title | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab |
|---|---|---|
| Arm/Group Description | Ovarian Cancer: Niraparib 200mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Triple Negative Breast Cancer: Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. |
| Measure Participants | 0 | 0 |
| Title | Phase 2: Duration of Response (DOR) |
|---|---|
| Description | From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the investigator until time of first documented progression or death by any cause. No maximum timeframe was specified in the protocol. |
| Time Frame | From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the Investigator until time of first documented progression. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Phase 2: Disease Control Rate (DCR) |
|---|---|
| Description | DCR is defined as the percentage of patients who achieved a CR or PR or stable disease (SD) using RECIST (v1.1) as assessed by the Investigator. |
| Time Frame | Up to 40 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed on all patients who received at least one dose of study medication. |
| Arm/Group Title | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab |
|---|---|---|
| Arm/Group Description | Ovarian Cancer: Niraparib 200mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Triple Negative Breast Cancer: Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. |
| Measure Participants | 53 | 55 |
| Number (90% Confidence Interval) [percentage of participants] |
58.5
835.7%
|
41.8
597.1%
|
| Title | Phase 2: Progression Free Survival (PFS) |
|---|---|
| Description | From date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression. No maximum timeframe was specified in the protocol. |
| Time Frame | From date of first dose to the earlier date of assessment of progression of death by any cause in the absence of progression. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Phase 2: Overall Survival (OS) |
|---|---|
| Description | Patients were followed off treatment every 90 days for survival status. Overall survival is defined as the time from first dose to the date of death by any cause. No maximum timeframe was specified in the protocol. |
| Time Frame | From date of first dose to the date of death by any cause. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Phase 1 and Phase 2: To Evaluate the Pharmacokinetics (PK) of Niraparib and Associated Major Metabolite M1 During Combination Treatment. |
|---|---|
| Description | Area Under the Curve (AUC), Minimum Concentration (Cmin), Maximum Concentration (Cmax), Clearance After Oral Administration (CL/F), Volume of Distribution After Oral Administration (Vz/F), AUC at Steady State (AUCss), Cmin at Steady State (Cmin,ss), Cmax at Steady State (Cmax,ss). |
| Time Frame | Approximately 9 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | AEs were collected up to 90 days following the last dose of study treatment, where the median duration of treatment was 3 months. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab | ||||
| Arm/Group Description | Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Niraparib 300 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Ovarian Cancer: Niraparib 200mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | Triple Negative Breast Cancer: Niraparib 200 mg/day orally (PO). Pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle. | ||||
All Cause Mortality |
||||||||
| Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/7 (71.4%) | 2/7 (28.6%) | 20/53 (37.7%) | 34/55 (61.8%) | ||||
Serious Adverse Events |
||||||||
| Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/7 (85.7%) | 4/7 (57.1%) | 20/53 (37.7%) | 22/55 (40%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anemia | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Febrile neutropenia | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Leukopenia | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Neutropenia | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Pancytopenia | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Thrombocytopenia | 1/7 (14.3%) | 3/7 (42.9%) | 2/53 (3.8%) | 3/55 (5.5%) | ||||
| Cardiac disorders | ||||||||
| Cardiac failure congestive | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Cardiac tamponade | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Pericardial effusion | 0/7 (0%) | 0/7 (0%) | 2/53 (3.8%) | 1/55 (1.8%) | ||||
| Tachycardia | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Endocrine disorders | ||||||||
| Adrenal insufficiency | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal distension | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Abdominal pain | 2/7 (28.6%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Ascites | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Colitis | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Constipation | 0/7 (0%) | 0/7 (0%) | 4/53 (7.5%) | 0/55 (0%) | ||||
| Intestinal perforation | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Nausea | 2/7 (28.6%) | 1/7 (14.3%) | 2/53 (3.8%) | 0/55 (0%) | ||||
| Obstruction gastric | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pancreatitis acute | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Small intestinal obstruction | 1/7 (14.3%) | 0/7 (0%) | 5/53 (9.4%) | 0/55 (0%) | ||||
| Vomiting | 1/7 (14.3%) | 0/7 (0%) | 4/53 (7.5%) | 0/55 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Chills | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Fatigue | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 2/55 (3.6%) | ||||
| Malaise | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Non-cardiac chest pain | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Oedema peripheral | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Pyrexia | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 3/55 (5.5%) | ||||
| Hepatobiliary disorders | ||||||||
| Bile duct stenosis | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Cholecystitis | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Infections and infestations | ||||||||
| Device related infection | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Gastroenteritis viral | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Lung infection | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Neutropenic sepsis | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Pneumonia | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 2/55 (3.6%) | ||||
| Stoma site infection | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Femur fracture | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Procedural pneumothorax | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Investigations | ||||||||
| Amylase increased | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Aspartate aminotransferase increased | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Blood alkaline phosphatase increased | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 2/55 (3.6%) | ||||
| Blood bilirubin increased | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Blood creatinine increased | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Liver function test increased | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Platelet count decreased | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Failure to thrive | 0/7 (0%) | 0/7 (0%) | 2/53 (3.8%) | 0/55 (0%) | ||||
| Hyperglycaemia | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Hyperkalaemia | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pain in extremity | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pathological fracture | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Malignant pleural effusion | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Metastases to central nervous system | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Nervous system disorders | ||||||||
| Cerebral haemorrhage | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Dizziness | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Encephalopathy | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Headache | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 3/55 (5.5%) | ||||
| Psychiatric disorders | ||||||||
| Mental status changes | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 3/55 (5.5%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory distress syndrome | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Dyspnoea | 0/7 (0%) | 1/7 (14.3%) | 2/53 (3.8%) | 1/55 (1.8%) | ||||
| Dyspnoea exertional | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Hypoxia | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 3/55 (5.5%) | ||||
| Pleural effusion | 0/7 (0%) | 1/7 (14.3%) | 1/53 (1.9%) | 4/55 (7.3%) | ||||
| Pneumonia aspiration | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pneumonitis | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pneumothorax | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pulmonary embolism | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Respiratory failure | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Decubitus ulcer | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Rash pruritic | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Vascular disorders | ||||||||
| Embolism | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Hypotension | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Orthostatic hypotension | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 1/55 (1.8%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Phase 1: Niraparib 200mg + Pembrolizumab | Phase 1: Niraparib 300mg + Pembrolizumab | Phase 2 OC: Niraparib 200mg + Pembrolizumab | Phase 2 TNBC: Niraparib 200mg + Pembrolizumab | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 7/7 (100%) | 52/53 (98.1%) | 54/55 (98.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 5/7 (71.4%) | 5/7 (71.4%) | 19/53 (35.8%) | 23/55 (41.8%) | ||||
| Leukocytosis | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Lymphopenia | 1/7 (14.3%) | 1/7 (14.3%) | 0/53 (0%) | 2/55 (3.6%) | ||||
| Neutropenia | 1/7 (14.3%) | 1/7 (14.3%) | 4/53 (7.5%) | 3/55 (5.5%) | ||||
| Thrombocytopenia | 1/7 (14.3%) | 4/7 (57.1%) | 14/53 (26.4%) | 13/55 (23.6%) | ||||
| Cardiac disorders | ||||||||
| Diastolic dysfunction | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Tachycardia | 2/7 (28.6%) | 1/7 (14.3%) | 2/53 (3.8%) | 2/55 (3.6%) | ||||
| Endocrine disorders | ||||||||
| Hyperthyroidism | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 3/55 (5.5%) | ||||
| Hypothyroidism | 2/7 (28.6%) | 0/7 (0%) | 7/53 (13.2%) | 6/55 (10.9%) | ||||
| Eye disorders | ||||||||
| Cataract | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Dry eye | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Lacrimation increased | 0/7 (0%) | 2/7 (28.6%) | 0/53 (0%) | 0/55 (0%) | ||||
| Ocular hyperaemia | 0/7 (0%) | 1/7 (14.3%) | 1/53 (1.9%) | 1/55 (1.8%) | ||||
| Vision blurred | 0/7 (0%) | 2/7 (28.6%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/7 (0%) | 0/7 (0%) | 3/53 (5.7%) | 0/55 (0%) | ||||
| Abdominal distension | 3/7 (42.9%) | 0/7 (0%) | 5/53 (9.4%) | 3/55 (5.5%) | ||||
| Abdominal pain | 3/7 (42.9%) | 0/7 (0%) | 15/53 (28.3%) | 7/55 (12.7%) | ||||
| Abdominal pain upper | 1/7 (14.3%) | 1/7 (14.3%) | 3/53 (5.7%) | 2/55 (3.6%) | ||||
| Ascites | 1/7 (14.3%) | 0/7 (0%) | 5/53 (9.4%) | 0/55 (0%) | ||||
| Colitis | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Constipation | 5/7 (71.4%) | 2/7 (28.6%) | 28/53 (52.8%) | 24/55 (43.6%) | ||||
| Diarrhoea | 2/7 (28.6%) | 2/7 (28.6%) | 15/53 (28.3%) | 12/55 (21.8%) | ||||
| Dry mouth | 1/7 (14.3%) | 0/7 (0%) | 4/53 (7.5%) | 4/55 (7.3%) | ||||
| Dyspepsia | 1/7 (14.3%) | 2/7 (28.6%) | 5/53 (9.4%) | 2/55 (3.6%) | ||||
| Gastrooesophageal reflux disease | 1/7 (14.3%) | 0/7 (0%) | 4/53 (7.5%) | 2/55 (3.6%) | ||||
| Nausea | 4/7 (57.1%) | 4/7 (57.1%) | 32/53 (60.4%) | 34/55 (61.8%) | ||||
| Noninfective gingivitis | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Stomatitis | 1/7 (14.3%) | 0/7 (0%) | 3/53 (5.7%) | 4/55 (7.3%) | ||||
| Toothache | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Vomiting | 4/7 (57.1%) | 2/7 (28.6%) | 20/53 (37.7%) | 12/55 (21.8%) | ||||
| General disorders | ||||||||
| Asthenia | 0/7 (0%) | 0/7 (0%) | 3/53 (5.7%) | 1/55 (1.8%) | ||||
| Chills | 0/7 (0%) | 0/7 (0%) | 3/53 (5.7%) | 2/55 (3.6%) | ||||
| Fatigue | 4/7 (57.1%) | 3/7 (42.9%) | 32/53 (60.4%) | 30/55 (54.5%) | ||||
| Local swelling | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Oedema peripheral | 3/7 (42.9%) | 1/7 (14.3%) | 2/53 (3.8%) | 4/55 (7.3%) | ||||
| Pain | 0/7 (0%) | 0/7 (0%) | 2/53 (3.8%) | 3/55 (5.5%) | ||||
| Peripheral swelling | 0/7 (0%) | 1/7 (14.3%) | 4/53 (7.5%) | 1/55 (1.8%) | ||||
| Pyrexia | 0/7 (0%) | 0/7 (0%) | 7/53 (13.2%) | 4/55 (7.3%) | ||||
| Infections and infestations | ||||||||
| Conjunctivitis | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Eye infection | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Laryngitis | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pneumonia | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 4/55 (7.3%) | ||||
| Sinusitis | 0/7 (0%) | 0/7 (0%) | 2/53 (3.8%) | 3/55 (5.5%) | ||||
| Upper respiratory tract infection | 0/7 (0%) | 1/7 (14.3%) | 1/53 (1.9%) | 5/55 (9.1%) | ||||
| Urinary tract infection | 0/7 (0%) | 0/7 (0%) | 7/53 (13.2%) | 9/55 (16.4%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Fall | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Overdose | 0/7 (0%) | 0/7 (0%) | 3/53 (5.7%) | 3/55 (5.5%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/7 (0%) | 0/7 (0%) | 8/53 (15.1%) | 10/55 (18.2%) | ||||
| Amylase increased | 0/7 (0%) | 0/7 (0%) | 3/53 (5.7%) | 2/55 (3.6%) | ||||
| Anticoagulation drug level increased | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Aspartate aminotransferase increased | 1/7 (14.3%) | 1/7 (14.3%) | 8/53 (15.1%) | 14/55 (25.5%) | ||||
| Blood alkaline phosphatase decreased | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Blood alkaline phosphatase increased | 2/7 (28.6%) | 0/7 (0%) | 6/53 (11.3%) | 9/55 (16.4%) | ||||
| Blood creatinine increased | 0/7 (0%) | 0/7 (0%) | 4/53 (7.5%) | 4/55 (7.3%) | ||||
| Creatinine renal clearance increased | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Electrocardiogram QT prolonged | 0/7 (0%) | 0/7 (0%) | 1/53 (1.9%) | 3/55 (5.5%) | ||||
| Lymphocyte count decreased | 1/7 (14.3%) | 1/7 (14.3%) | 2/53 (3.8%) | 10/55 (18.2%) | ||||
| Neutrophil count decreased | 0/7 (0%) | 0/7 (0%) | 7/53 (13.2%) | 6/55 (10.9%) | ||||
| Platelet count decreased | 0/7 (0%) | 2/7 (28.6%) | 7/53 (13.2%) | 9/55 (16.4%) | ||||
| Troponin increased | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Weight decreased | 1/7 (14.3%) | 1/7 (14.3%) | 8/53 (15.1%) | 3/55 (5.5%) | ||||
| White blood cell count decreased | 1/7 (14.3%) | 1/7 (14.3%) | 4/53 (7.5%) | 6/55 (10.9%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 2/7 (28.6%) | 3/7 (42.9%) | 17/53 (32.1%) | 14/55 (25.5%) | ||||
| Dehydration | 1/7 (14.3%) | 3/7 (42.9%) | 6/53 (11.3%) | 6/55 (10.9%) | ||||
| Hyperglycaemia | 0/7 (0%) | 1/7 (14.3%) | 5/53 (9.4%) | 5/55 (9.1%) | ||||
| Hypoalbuminaemia | 3/7 (42.9%) | 0/7 (0%) | 1/53 (1.9%) | 2/55 (3.6%) | ||||
| Hypocalcaemia | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 4/55 (7.3%) | ||||
| Hypokalaemia | 3/7 (42.9%) | 1/7 (14.3%) | 6/53 (11.3%) | 6/55 (10.9%) | ||||
| Hypomagnesaemia | 3/7 (42.9%) | 1/7 (14.3%) | 7/53 (13.2%) | 5/55 (9.1%) | ||||
| Hyponatraemia | 4/7 (57.1%) | 3/7 (42.9%) | 6/53 (11.3%) | 6/55 (10.9%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/7 (14.3%) | 0/7 (0%) | 7/53 (13.2%) | 9/55 (16.4%) | ||||
| Back pain | 1/7 (14.3%) | 1/7 (14.3%) | 8/53 (15.1%) | 8/55 (14.5%) | ||||
| Flank pain | 0/7 (0%) | 0/7 (0%) | 3/53 (5.7%) | 3/55 (5.5%) | ||||
| Muscular weakness | 0/7 (0%) | 2/7 (28.6%) | 2/53 (3.8%) | 3/55 (5.5%) | ||||
| Musculoskeletal chest pain | 0/7 (0%) | 1/7 (14.3%) | 2/53 (3.8%) | 3/55 (5.5%) | ||||
| Musculoskeletal pain | 0/7 (0%) | 0/7 (0%) | 2/53 (3.8%) | 5/55 (9.1%) | ||||
| Myalgia | 0/7 (0%) | 0/7 (0%) | 7/53 (13.2%) | 3/55 (5.5%) | ||||
| Neck pain | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 3/55 (5.5%) | ||||
| Pain in extremity | 1/7 (14.3%) | 1/7 (14.3%) | 1/53 (1.9%) | 6/55 (10.9%) | ||||
| Nervous system disorders | ||||||||
| Ataxia | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Dizziness | 2/7 (28.6%) | 1/7 (14.3%) | 6/53 (11.3%) | 6/55 (10.9%) | ||||
| Dysgeusia | 1/7 (14.3%) | 3/7 (42.9%) | 4/53 (7.5%) | 6/55 (10.9%) | ||||
| Headache | 2/7 (28.6%) | 2/7 (28.6%) | 14/53 (26.4%) | 14/55 (25.5%) | ||||
| Neuropathy peripheral | 0/7 (0%) | 0/7 (0%) | 3/53 (5.7%) | 4/55 (7.3%) | ||||
| Peripheral sensory neuropathy | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/7 (0%) | 3/7 (42.9%) | 3/53 (5.7%) | 6/55 (10.9%) | ||||
| Confusional state | 1/7 (14.3%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Depression | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Insomnia | 2/7 (28.6%) | 3/7 (42.9%) | 11/53 (20.8%) | 13/55 (23.6%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 3/55 (5.5%) | ||||
| Chronic kidney disease | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Costovertebral angle tenderness | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Haematuria | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Proteinuria | 1/7 (14.3%) | 0/7 (0%) | 2/53 (3.8%) | 1/55 (1.8%) | ||||
| Reproductive system and breast disorders | ||||||||
| Breast tenderness | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Pelvic pain | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Vaginal haemorrhage | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/7 (14.3%) | 2/7 (28.6%) | 9/53 (17%) | 18/55 (32.7%) | ||||
| Dyspnoea | 3/7 (42.9%) | 4/7 (57.1%) | 11/53 (20.8%) | 20/55 (36.4%) | ||||
| Dyspnoea exertional | 1/7 (14.3%) | 1/7 (14.3%) | 2/53 (3.8%) | 2/55 (3.6%) | ||||
| Epistaxis | 0/7 (0%) | 2/7 (28.6%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Hypoxia | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 2/55 (3.6%) | ||||
| Nasal congestion | 0/7 (0%) | 1/7 (14.3%) | 2/53 (3.8%) | 5/55 (9.1%) | ||||
| Oropharyngeal pain | 2/7 (28.6%) | 0/7 (0%) | 2/53 (3.8%) | 1/55 (1.8%) | ||||
| Pleural effusion | 1/7 (14.3%) | 0/7 (0%) | 3/53 (5.7%) | 3/55 (5.5%) | ||||
| Pleuritic pain | 1/7 (14.3%) | 0/7 (0%) | 0/53 (0%) | 0/55 (0%) | ||||
| Productive cough | 0/7 (0%) | 0/7 (0%) | 2/53 (3.8%) | 3/55 (5.5%) | ||||
| Pulmonary hypertension | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Upper-airway cough syndrome | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 0/55 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermatitis contact | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 1/55 (1.8%) | ||||
| Dry skin | 1/7 (14.3%) | 2/7 (28.6%) | 1/53 (1.9%) | 2/55 (3.6%) | ||||
| Erythema | 0/7 (0%) | 1/7 (14.3%) | 2/53 (3.8%) | 1/55 (1.8%) | ||||
| Night sweats | 1/7 (14.3%) | 0/7 (0%) | 1/53 (1.9%) | 2/55 (3.6%) | ||||
| Onychoclasis | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Onychomadesis | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Photosensitivity reaction | 1/7 (14.3%) | 1/7 (14.3%) | 1/53 (1.9%) | 2/55 (3.6%) | ||||
| Pruritus | 0/7 (0%) | 1/7 (14.3%) | 9/53 (17%) | 4/55 (7.3%) | ||||
| Rash | 1/7 (14.3%) | 1/7 (14.3%) | 6/53 (11.3%) | 7/55 (12.7%) | ||||
| Rash maculo-papular | 0/7 (0%) | 0/7 (0%) | 2/53 (3.8%) | 3/55 (5.5%) | ||||
| Skin lesion | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 0/55 (0%) | ||||
| Vascular disorders | ||||||||
| Hot flush | 0/7 (0%) | 1/7 (14.3%) | 0/53 (0%) | 7/55 (12.7%) | ||||
| Hypertension | 0/7 (0%) | 0/7 (0%) | 5/53 (9.4%) | 4/55 (7.3%) | ||||
| Lymphoedema | 0/7 (0%) | 0/7 (0%) | 0/53 (0%) | 3/55 (5.5%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Neither Institution nor Investigator will submit for publication or public disclosure any publication or disclosure based on the results of the Study until after the first to occur of (a) publication of the Multi-Center Clinical Trial results; (b) notification by Sponsor that the Multi-Center Clinical Trial submission is no longer planned; or (c) the eighteen (18) month anniversary of the completion or early termination of the Multi-Center Clinical Trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
| GSKClinicalSupportHD@gsk.com |
- 213363
- 3000-PN162-01-001