A Study Evaluating the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Adults With Stage III Non-Small Cell Lung Cancer (NSCLC)
Sponsor
AbbVie (Industry)
Overall Status
Terminated
CT.gov ID
NCT02412371
Collaborator
(none)
48
12
4
51.2
4
0.1
Study Details
Study Description
Brief Summary
This study seeks to establish
-
the recommended Phase 2 dose (RPTD) of veliparib in combination with concurrent paclitaxel/carboplatin-based chemoradiotherapy (CRT) and consolidation with paclitaxel/carboplatin-based chemotherapy (Phase 1 portion), and
-
to assess whether the addition of oral veliparib versus placebo to paclitaxel/carboplatin-based chemoradiotherapy with paclitaxel/carboplatin consolidation will improve progression-free survival (PFS) in adults with Stage III non-small cell lung cancer (Phase 2 portion).
A strategy decision was made not to proceed to Phase 2 portion of this study due to change in standard of care.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This was to be a 2-phase study consisting of
-
A Phase 1, dose escalation study of veliparib to determine a RPTD for combination with concurrent paclitaxel/carboplatin-based CRT and paclitaxel/carboplatin-based consolidation chemotherapy; followed by
-
A Phase 2, randomized, double-blinded study to determine whether veliparib improved outcome relative to placebo when added to paclitaxel/carboplatin based CRT followed by consolidation paclitaxel/carboplatin in adults with previously untreated Stage III NSCLC.
In the dose escalation phase (Phase 1) of the study participants will be assigned to ascending doses of veliparib in combination with carboplatin, paclitaxel, and thoracic radiotherapy for 7 weeks following a traditional "3 + 3" design. The first cohort of at least 3 - 6 participants will receive veliparib 60 mg twice a day (BID) throughout CRT. Dose limiting toxicity (DLT) events will be collected for each dosing cohort until a new dosing cohort is opened or until the RPTD is identified. Participants will also receive a consolidation dose of veliparib of 120 mg BID + carboplatin and paclitaxel for up to two 21-day cycles. Once the concurrent CRT RPTD is identified, an additional cohort will be enrolled to explore the tolerability of a consolidation dose of veliparib at 240 mg BID + carboplatin + paclitaxel for up to two 21-day cycles.
Following the dose escalation portion of the study, the RPTD will be determined by the sponsor and the Phase 2 portion of the study will begin with patient randomization in a 1:1:1 ratio to concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/veliparib, concurrent paclitaxel/carboplatin/radiotherapy/veliparib followed by consolidation paclitaxel/carboplatin/placebo, or concurrent paclitaxel/carboplatin/radiotherapy/placebo followed by consolidation paclitaxel/carboplatin/placebo. Randomization will be stratified by tumor volume (≤ 90 versus
90 cm³) and smoking history (current smoker versus former smoker versus never smoked).
Phase 2 was not carried out since during the study there was a change in standard of care for patients with newly diagnosed, unresectable Stage III NSCLC.
Study Design
Study Type:
Interventional
Actual Enrollment
:
48 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
In the dose escalation phase (Phase 1) of the study participants will be enrolled sequentially to receive ascending dose of veliparib in combination with carboplatin + paclitaxel + thoracic radiotherapy.
In the Phase 2 portion of the study participants were to be randomized in a 1:1:1 ratio to one of three treatment arms.In the dose escalation phase (Phase 1) of the study participants will be enrolled sequentially to receive ascending dose of veliparib in combination with carboplatin + paclitaxel + thoracic radiotherapy.
In the Phase 2 portion of the study participants were to be randomized in a 1:1:1 ratio to one of three treatment arms.
Masking:
None (Open Label)
Masking Description:
All participants will be treated with open-label paclitaxel and carboplatin (Phase 1 and Phase 2).
Participants in Phase 1 will be treated with open-label veliparib. In Phase 2, the Sponsor, Investigator, study site personnel and participant were to be be blinded to each participant's treatment with veliparib or placebo throughout the course of the study.
Primary Purpose:
Treatment
Official Title:
A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in Subjects With Stage III Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date
:
Apr 30, 2015
Actual Primary Completion Date
:
Aug 5, 2019
Actual Study Completion Date
:
Aug 5, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1: Veliparib + Carboplatin + Paclitaxel + Radiotherapy Participants in Phase 1 will be sequentially assigned to ascending dose levels of 60 mg, 80 mg, 120 mg, 200 mg, and 240 mg of twice daily (BID) veliparib in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
Drug: Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Drug: Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Drug: Veliparib
Capsule for oral administration
Other Names:
Radiation: Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
|
| Experimental: Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Veliparib Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of veliparib 120 mg or 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
Drug: Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Drug: Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Drug: Veliparib
Capsule for oral administration
Other Names:
Radiation: Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
|
| Experimental: Phase 2: Veliparib + CRT -> Paclitaxel/Carboplatin/Placebo Participants will receive veliparib at the recommended phase 2 dose determined in Phase 1 in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
Drug: Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Drug: Placebo for Veliparib
Capsule for oral administration
Drug: Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Drug: Veliparib
Capsule for oral administration
Other Names:
Radiation: Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
|
| Active Comparator: Phase 2: Placebo + CRT -> Paclitaxel/Carboplatin/Placebo Participants will receive placebo to veliparib with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent chemoradiotherapy participants will receive up to 2 cycles of consolidation therapy consisting of placebo to veliparib BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
Drug: Paclitaxel
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Drug: Placebo for Veliparib
Capsule for oral administration
Drug: Carboplatin
Administered via intravenous infusion on Day 1 of each treatment week (concurrent CRT) / cycle (consolidation)
Radiation: Radiotherapy
Radiation treatment with total dose of 60 - 63 Gy administered on Days 1 to 5 of each week for 7 weeks
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-limiting Toxicities (DLTs) [For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy.]
DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of >3 weeks or early discontinuation (DC) of RT (total dose <50 Gy) ≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of >7 days despite medical management, neutropenia for >7 days or neutropenic fever or thrombocytopenia ≥G2 seizure G4 diarrhea or nausea/vomiting despite antiemetic therapy for >48 hours Any other toxicity resulting in delay in RT, CT or veliparib >14 days or early DC of RT Other nonhematologic toxicities ≥G3, except anorexia, fatigue, G3 infection, G3 aspartate/alanine transferase (AST/ALT) elevations ≤7 days, infusion reactions, G3/4 lymphopenia or electrolyte abnormalities corrected to ≤G2 in <48 hours
Secondary Outcome Measures
- Objective Response Rate [Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.]
Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders. Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Response must have been confirmed 4 weeks after the first documentation.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Participants with histologically or cytologically confirmed Stage III non-small cell lung cancer (NSCLC).
-
Participants in the randomized portion of the study must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 criteria.
-
Participants must have V20 (volume of lung to receive 20 Gy radiotherapy according to simulation) < 35%.
-
Participant must have an Eastern Cooperative Oncology Group (ECOG) performance score of 0 - 1.
-
Participant must have adequate hematologic, renal, hepatic, and lung function.
-
Participant must consent to provide archived tissue or cytology sample of NSCLC lesion for analysis.
Exclusion Criteria:
-
Participants with prior chemotherapy or radiotherapy (RT) for current NSCLC. Participants curatively treated for past early stage NSCLC greater than 3 years ago may be included.
-
Participants with prior exposure to poly-adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors.
-
Participants with known hypersensitivity to carboplatin, paclitaxel, or formulations containing polyethoxylated castor oil (Cremophor).
-
Participants with prior mediastinal or thoracic radiotherapy. Prior tangential radiotherapy to prior breast cancer is acceptable.
-
Participants with major surgery in the 4 weeks prior to randomization (Video-assisted thoracoscopic surgery (VATS) and/or mediastinoscopy is not considered major surgery).
-
Participants with a previous or concurrent malignancy except for treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient received potentially curative treatment and has been disease-free for 3 years or is considered cured by the investigator if has been disease-free for less than 3 years.
-
Participant is pregnant or lactating.
-
Participant with sensory peripheral neuropathy of ≥ Grade 2 at baseline, unable to swallow medication, or participants with prior history of seizure within the prior 12 months.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ucsd /Id# 133037 | La Jolla | California | United States | 92093 |
| 2 | Christiana Care Health Service /ID# 133486 | Newark | Delaware | United States | 19713 |
| 3 | University of Chicago /ID# 133828 | Chicago | Illinois | United States | 60637-1443 |
| 4 | Univ Maryland School Medicine /ID# 132944 | Baltimore | Maryland | United States | 21201 |
| 5 | Dana-Farber Cancer Institute /ID# 133494 | Boston | Massachusetts | United States | 02215 |
| 6 | SUNY Upstate Medical University - Downtown /ID# 133492 | Syracuse | New York | United States | 13210 |
| 7 | Unc /Id# 133496 | Chapel Hill | North Carolina | United States | 27599 |
| 8 | Duke University Medical Center /ID# 133497 | Durham | North Carolina | United States | 27710-3000 |
| 9 | Wake Forest Univ HS /ID# 134608 | Winston-Salem | North Carolina | United States | 27157 |
| 10 | Rhode Island Hospital /ID# 133493 | Providence | Rhode Island | United States | 02903 |
| 11 | The Miriam Hospital /ID# 133910 | Providence | Rhode Island | United States | 02906 |
| 12 | University of Virginia /ID# 133495 | Charlottesville | Virginia | United States | 22908 |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02412371
Other Study ID Numbers:
- M14-360
- 2016-001659-32
First Posted:
Apr 9, 2015
Last Update Posted:
Jul 22, 2020
Last Verified:
Jul 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by AbbVie
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study enrolled 48 participants at 10 sites in the United States. The study was designed as a 2-phase study consisting of a Phase 1, dose escalation of veliparib in combination with concurrent chemoradiotherapy (CRT) and consolidation chemotherapy (CT) and a Phase 2, randomized, double-blinded study. |
|---|---|
| Pre-assignment Detail | Participants in Phase 1 were sequentially assigned to ascending dose levels of veliparib in combination with carboplatin/paclitaxel chemoradiotherapy. Phase 2 was not conducted since there was a change in standard of care for newly diagnosed, unresectable Stage III non-small cell lung cancer (NSCLC). Results are reported for Phase 1. |
| Arm/Group Title | Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 60 mg veliparib twice daily (BID) in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy (RT) for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 80 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 120 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 200 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
| Period Title: Overall Study | ||||||
| STARTED | 7 | 9 | 7 | 8 | 12 | 5 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 7 | 9 | 7 | 8 | 12 | 5 |
Baseline Characteristics
| Arm/Group Title | Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 60 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 80 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 120 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 200 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Total of all reporting groups |
| Overall Participants | 7 | 9 | 7 | 8 | 12 | 5 | 48 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
69.1
(6.39)
|
65.7
(7.55)
|
66.9
(9.84)
|
59.8
(6.07)
|
67.3
(9.39)
|
65.6
(11.84)
|
65.8
(8.60)
|
| Age, Customized (Count of Participants) | |||||||
| 40 - < 60 years |
0
0%
|
1
11.1%
|
2
28.6%
|
3
37.5%
|
2
16.7%
|
1
20%
|
9
18.8%
|
| ≥ 60 years |
7
100%
|
8
88.9%
|
5
71.4%
|
5
62.5%
|
10
83.3%
|
4
80%
|
39
81.3%
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
4
57.1%
|
6
66.7%
|
5
71.4%
|
6
75%
|
5
41.7%
|
3
60%
|
29
60.4%
|
| Male |
3
42.9%
|
3
33.3%
|
2
28.6%
|
2
25%
|
7
58.3%
|
2
40%
|
19
39.6%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||
| White |
6
85.7%
|
9
100%
|
6
85.7%
|
8
100%
|
11
91.7%
|
3
60%
|
43
89.6%
|
| Black |
1
14.3%
|
0
0%
|
1
14.3%
|
0
0%
|
1
8.3%
|
2
40%
|
5
10.4%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Score (Count of Participants) | |||||||
| Grade 0 (Fully active) |
3
42.9%
|
3
33.3%
|
3
42.9%
|
4
50%
|
6
50%
|
4
80%
|
23
47.9%
|
| Grade 1 (Restricted but ambulatory) |
4
57.1%
|
6
66.7%
|
4
57.1%
|
4
50%
|
6
50%
|
1
20%
|
25
52.1%
|
Outcome Measures
| Title | Number of Participants With Dose-limiting Toxicities (DLTs) |
|---|---|
| Description | DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of >3 weeks or early discontinuation (DC) of RT (total dose <50 Gy) ≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of >7 days despite medical management, neutropenia for >7 days or neutropenic fever or thrombocytopenia ≥G2 seizure G4 diarrhea or nausea/vomiting despite antiemetic therapy for >48 hours Any other toxicity resulting in delay in RT, CT or veliparib >14 days or early DC of RT Other nonhematologic toxicities ≥G3, except anorexia, fatigue, G3 infection, G3 aspartate/alanine transferase (AST/ALT) elevations ≤7 days, infusion reactions, G3/4 lymphopenia or electrolyte abnormalities corrected to ≤G2 in <48 hours |
| Time Frame | For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of veliparib |
| Arm/Group Title | Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 60 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 80 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 120 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 200 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
| Measure Participants | 7 | 9 | 7 | 8 | 12 | 5 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
0
0%
|
2
40%
|
| Title | Objective Response Rate |
|---|---|
| Description | Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders. Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Response must have been confirmed 4 weeks after the first documentation. |
| Time Frame | Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of veliparib and with at least one post-baseline tumor assessment |
| Arm/Group Title | Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 60 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 80 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 120 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 200 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
| Measure Participants | 6 | 8 | 7 | 8 | 11 | 3 |
| Number (95% Confidence Interval) [percentage of participants] |
50.0
714.3%
|
50.0
555.6%
|
100.0
1428.6%
|
62.5
781.3%
|
72.7
605.8%
|
0.0
0%
|
| Title | Progression-free Survival |
|---|---|
| Description | Progression-free survival (PFS) was defined as the time from first dose of study drug to the date of earliest radiographic disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death, and was calculated using Kaplan-Meier methods. All radiographic disease progression was included regardless whether the event occurred while the participant was taking study drug or had previously discontinued study drug. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment. Participants with no post-baseline disease assessment were censored at first dose date plus 1 day. Progressive disease (PD) was defined as at least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. |
| Time Frame | From first dose until end of study; maximum time on follow-up was approximately 46 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received veliparib; PFS was pre-specified in the Protocol as a primary endpoint in Phase 2, which was not conducted. For Phase 1 PFS was not a pre-specified endpoint, and was only analyzed for all treatment cohorts combined due to the small sample sizes within each cohort. |
| Arm/Group Title | Total |
|---|---|
| Arm/Group Description | Participants received veliparib twice daily (BID) in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 or 240 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
| Measure Participants | 48 |
| Median (95% Confidence Interval) [months] |
19.6
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival (OS) was defined as the time from the participant's first dose of study drug to the date of death, and was calculated using Kaplan-Meier methods. Participants who did not die were censored at the date of last study visit or the last known date to be alive, whichever was later. |
| Time Frame | From first dose of study drug until end of study; maximum time on follow-up was approximately 46 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received veliparib; OS was pre-specified in the Protocol as a secondary endpoint in Phase 2, which was not conducted. For Phase 1 OS was not a pre-specified endpoint, and was only analyzed for all treatment cohorts combined due to the small sample sizes within each cohort. |
| Arm/Group Title | Total |
|---|---|
| Arm/Group Description | Participants received veliparib twice daily (BID) in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 or 240 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
| Measure Participants | 48 |
| Median (95% Confidence Interval) [months] |
32.6
|
| Title | Duration of Overall Response (DOR) |
|---|---|
| Description | Duration of overall response was defined as time from the date of first response (CR or PR) to the earliest documentation of radiographic progressive disease or death due to disease progression, calculated using Kaplan-Meier methods. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment. |
| Time Frame | Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of veliparib with at least 1 post-baseline tumor assessment and a confirmed response; DOR was prespecified as a secondary endpoint in Phase 2, which was not conducted. For Phase 1 DOR was not a prespecified endpoint and was only analyzed for all cohorts combined due to the small sample size of each cohort. |
| Arm/Group Title | Total |
|---|---|
| Arm/Group Description | Participants received veliparib twice daily (BID) in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 or 240 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. |
| Measure Participants | 27 |
| Median (95% Confidence Interval) [months] |
30.4
|
Adverse Events
| Time Frame | Adverse events were collected from the first dose of study drug to 30 days after the last dose of study drug; maximum duration of treatment was 14 weeks. Deaths were collected from the first dose of study drug through the end of study, up to 46 months. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT | ||||||
| Arm/Group Description | Participants received 60 mg veliparib BID in combination with carboplatin at an area under the concentration-time curve (AUC) 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 80 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 120 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 200 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 120 mg BID with carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | Participants received 240 mg veliparib BID in combination with carboplatin at an AUC 2 mg/mL/min and paclitaxel 45 mg/m² once a week plus thoracic radiotherapy for 7 weeks. After completion of concurrent CRT participants received up to 2 cycles of consolidation therapy consisting of veliparib 240 mg BID, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m² administered on Day 1 of each 21-day cycle. | ||||||
All Cause Mortality |
||||||||||||
| Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/7 (71.4%) | 3/9 (33.3%) | 1/7 (14.3%) | 3/8 (37.5%) | 6/12 (50%) | 3/5 (60%) | ||||||
Serious Adverse Events |
||||||||||||
| Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/7 (28.6%) | 5/9 (55.6%) | 4/7 (57.1%) | 3/8 (37.5%) | 3/12 (25%) | 2/5 (40%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| FEBRILE NEUTROPENIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 3 |
| Cardiac disorders | ||||||||||||
| CARDIAC ARREST | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| CARDIAC TAMPONADE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| DIARRHOEA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| NAUSEA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| OESOPHAGEAL OBSTRUCTION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| OESOPHAGEAL STENOSIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| OESOPHAGITIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| VOMITING | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| General disorders | ||||||||||||
| NON-CARDIAC CHEST PAIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PYREXIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Infections and infestations | ||||||||||||
| PNEUMONIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| SEPSIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||
| RADIATION PNEUMONITIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 2/12 (16.7%) | 2 | 0/5 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||
| DEHYDRATION | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 2 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 2 | 0/5 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| BACK PAIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| HAEMOPTYSIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PNEUMONIA ASPIRATION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PULMONARY OEDEMA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
| Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT | Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 9/9 (100%) | 7/7 (100%) | 8/8 (100%) | 12/12 (100%) | 5/5 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| ANAEMIA | 3/7 (42.9%) | 9 | 3/9 (33.3%) | 4 | 3/7 (42.9%) | 6 | 1/8 (12.5%) | 3 | 6/12 (50%) | 11 | 3/5 (60%) | 10 |
| FEBRILE NEUTROPENIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| LEUKOCYTOSIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| LEUKOPENIA | 3/7 (42.9%) | 3 | 4/9 (44.4%) | 7 | 3/7 (42.9%) | 12 | 2/8 (25%) | 6 | 7/12 (58.3%) | 16 | 4/5 (80%) | 9 |
| LYMPHOPENIA | 1/7 (14.3%) | 3 | 2/9 (22.2%) | 5 | 1/7 (14.3%) | 1 | 3/8 (37.5%) | 4 | 5/12 (41.7%) | 17 | 2/5 (40%) | 4 |
| NEUTROPENIA | 3/7 (42.9%) | 4 | 6/9 (66.7%) | 7 | 6/7 (85.7%) | 12 | 4/8 (50%) | 6 | 9/12 (75%) | 15 | 4/5 (80%) | 7 |
| THROMBOCYTOPENIA | 2/7 (28.6%) | 2 | 6/9 (66.7%) | 8 | 3/7 (42.9%) | 7 | 3/8 (37.5%) | 6 | 9/12 (75%) | 18 | 4/5 (80%) | 6 |
| Cardiac disorders | ||||||||||||
| ANGINA PECTORIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| ATRIAL FIBRILLATION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PALPITATIONS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| SINUS TACHYCARDIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| TACHYCARDIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 2 | 0/8 (0%) | 0 | 1/12 (8.3%) | 2 | 0/5 (0%) | 0 |
| VENTRICULAR TACHYCARDIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Ear and labyrinth disorders | ||||||||||||
| EXTERNAL EAR PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| TINNITUS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Eye disorders | ||||||||||||
| DRY EYE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| VISION BLURRED | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| VITREOUS FLOATERS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||
| ABDOMINAL DISTENSION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| ABDOMINAL PAIN LOWER | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| CONSTIPATION | 4/7 (57.1%) | 5 | 2/9 (22.2%) | 2 | 2/7 (28.6%) | 3 | 4/8 (50%) | 9 | 3/12 (25%) | 3 | 4/5 (80%) | 5 |
| DIARRHOEA | 4/7 (57.1%) | 4 | 2/9 (22.2%) | 2 | 2/7 (28.6%) | 4 | 1/8 (12.5%) | 1 | 4/12 (33.3%) | 6 | 1/5 (20%) | 1 |
| DRY MOUTH | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 2/12 (16.7%) | 3 | 1/5 (20%) | 1 |
| DYSPEPSIA | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| DYSPHAGIA | 5/7 (71.4%) | 7 | 1/9 (11.1%) | 1 | 4/7 (57.1%) | 4 | 7/8 (87.5%) | 12 | 3/12 (25%) | 3 | 2/5 (40%) | 3 |
| FLATULENCE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 2 | 1/8 (12.5%) | 1 | 2/12 (16.7%) | 2 | 1/5 (20%) | 1 |
| GINGIVAL BLEEDING | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| HAEMORRHOIDS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| NAUSEA | 3/7 (42.9%) | 4 | 5/9 (55.6%) | 8 | 5/7 (71.4%) | 10 | 4/8 (50%) | 6 | 10/12 (83.3%) | 16 | 5/5 (100%) | 9 |
| ODYNOPHAGIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 2/8 (25%) | 2 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| OESOPHAGEAL PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| OESOPHAGEAL STENOSIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| OESOPHAGEAL ULCER | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| OESOPHAGITIS | 4/7 (57.1%) | 4 | 6/9 (66.7%) | 7 | 4/7 (57.1%) | 7 | 4/8 (50%) | 5 | 9/12 (75%) | 10 | 3/5 (60%) | 4 |
| ORAL PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| STOMATITIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 1/5 (20%) | 1 |
| VOMITING | 1/7 (14.3%) | 1 | 4/9 (44.4%) | 6 | 2/7 (28.6%) | 3 | 2/8 (25%) | 5 | 4/12 (33.3%) | 7 | 3/5 (60%) | 8 |
| General disorders | ||||||||||||
| ASTHENIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| CATHETER SITE PAIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| CHEST PAIN | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 2 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| CHILLS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 2/12 (16.7%) | 2 | 0/5 (0%) | 0 |
| EXTRAVASATION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| FATIGUE | 6/7 (85.7%) | 9 | 6/9 (66.7%) | 6 | 5/7 (71.4%) | 8 | 3/8 (37.5%) | 3 | 7/12 (58.3%) | 11 | 5/5 (100%) | 7 |
| FEELING HOT | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| GRAVITATIONAL OEDEMA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| INJECTION SITE REACTION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| LOCALISED OEDEMA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| MALAISE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| MEDICAL DEVICE SITE ERYTHEMA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| MUCOSAL DRYNESS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| MUCOSAL INFLAMMATION | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| NON-CARDIAC CHEST PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 3/12 (25%) | 4 | 1/5 (20%) | 2 |
| OEDEMA PERIPHERAL | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| PERFORMANCE STATUS DECREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PERIPHERAL SWELLING | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 2/8 (25%) | 2 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PYREXIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 3 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 1/5 (20%) | 1 |
| SWELLING FACE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| Immune system disorders | ||||||||||||
| DRUG HYPERSENSITIVITY | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| Infections and infestations | ||||||||||||
| BACTERAEMIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| BRONCHITIS | 0/7 (0%) | 0 | 3/9 (33.3%) | 3 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| CANDIDA INFECTION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| CATHETER SITE CELLULITIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| CATHETER SITE INFECTION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| DIARRHOEA INFECTIOUS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| FUNGAL INFECTION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| HERPES SIMPLEX OESOPHAGITIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| HERPES ZOSTER | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| INFLUENZA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| LARYNGITIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| NASOPHARYNGITIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| OESOPHAGEAL CANDIDIASIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| ORAL CANDIDIASIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| OTITIS EXTERNA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| PNEUMONIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 3/12 (25%) | 3 | 0/5 (0%) | 0 |
| UPPER RESPIRATORY TRACT INFECTION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| URINARY TRACT INFECTION | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| VULVOVAGINAL CANDIDIASIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||||
| FALL | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| INCISION SITE COMPLICATION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| INFUSION RELATED REACTION | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| MUSCLE STRAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| RADIATION INJURY | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| RADIATION OESOPHAGITIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 2 | 1/12 (8.3%) | 2 | 0/5 (0%) | 0 |
| RADIATION PNEUMONITIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| RADIATION SKIN INJURY | 2/7 (28.6%) | 4 | 2/9 (22.2%) | 2 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 2/12 (16.7%) | 2 | 1/5 (20%) | 1 |
| Investigations | ||||||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 1/5 (20%) | 1 |
| BLOOD ALKALINE PHOSPHATASE INCREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| BLOOD BILIRUBIN INCREASED | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| BLOOD CREATININE INCREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| BLOOD GLUCOSE INCREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 2 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| BLOOD PRESSURE INCREASED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| ELECTROCARDIOGRAM QT PROLONGED | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 3 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| WEIGHT DECREASED | 2/7 (28.6%) | 2 | 2/9 (22.2%) | 3 | 3/7 (42.9%) | 4 | 3/8 (37.5%) | 5 | 5/12 (41.7%) | 11 | 4/5 (80%) | 5 |
| Metabolism and nutrition disorders | ||||||||||||
| DECREASED APPETITE | 3/7 (42.9%) | 3 | 5/9 (55.6%) | 5 | 3/7 (42.9%) | 3 | 2/8 (25%) | 2 | 2/12 (16.7%) | 6 | 3/5 (60%) | 3 |
| DEHYDRATION | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 2 | 4/7 (57.1%) | 5 | 2/8 (25%) | 3 | 5/12 (41.7%) | 5 | 0/5 (0%) | 0 |
| HYPERGLYCAEMIA | 0/7 (0%) | 0 | 3/9 (33.3%) | 3 | 1/7 (14.3%) | 2 | 0/8 (0%) | 0 | 1/12 (8.3%) | 5 | 0/5 (0%) | 0 |
| HYPERKALAEMIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| HYPERLIPIDAEMIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| HYPERMAGNESAEMIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| HYPERTRIGLYCERIDAEMIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| HYPOALBUMINAEMIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 2/7 (28.6%) | 2 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 2/5 (40%) | 3 |
| HYPOCALCAEMIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| HYPOKALAEMIA | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 3 | 2/8 (25%) | 3 | 4/12 (33.3%) | 6 | 1/5 (20%) | 1 |
| HYPOMAGNESAEMIA | 2/7 (28.6%) | 2 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 2 | 1/8 (12.5%) | 1 | 2/12 (16.7%) | 3 | 1/5 (20%) | 1 |
| HYPONATRAEMIA | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 2/12 (16.7%) | 2 | 1/5 (20%) | 2 |
| HYPOPHAGIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 2 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| LACTIC ACIDOSIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||
| ARTHRALGIA | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 2/12 (16.7%) | 2 | 1/5 (20%) | 1 |
| ARTHRITIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| BACK PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 1/5 (20%) | 1 |
| BONE PAIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| COSTOCHONDRITIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| FLANK PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| JOINT SWELLING | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| MUSCLE SPASMS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 2 | 1/8 (12.5%) | 2 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| MUSCULAR WEAKNESS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| MUSCULOSKELETAL PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| MYALGIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 2/7 (28.6%) | 2 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| NECK PAIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 1/5 (20%) | 1 |
| PAIN IN EXTREMITY | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| TENDONITIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| BENIGN BREAST NEOPLASM | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| TUMOUR PAIN | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Nervous system disorders | ||||||||||||
| DIZZINESS | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 2/7 (28.6%) | 2 | 3/8 (37.5%) | 4 | 4/12 (33.3%) | 4 | 1/5 (20%) | 1 |
| DIZZINESS POSTURAL | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| DYSGEUSIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 2/7 (28.6%) | 2 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 1/5 (20%) | 1 |
| HEADACHE | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 3 | 3/7 (42.9%) | 6 | 4/8 (50%) | 4 | 1/12 (8.3%) | 2 | 0/5 (0%) | 0 |
| NEURALGIA | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PARAESTHESIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| PERIPHERAL MOTOR NEUROPATHY | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PERIPHERAL SENSORY NEUROPATHY | 2/7 (28.6%) | 4 | 1/9 (11.1%) | 1 | 2/7 (28.6%) | 3 | 2/8 (25%) | 3 | 1/12 (8.3%) | 1 | 2/5 (40%) | 4 |
| SYNCOPE | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| TASTE DISORDER | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| TREMOR | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| Psychiatric disorders | ||||||||||||
| ANXIETY | 2/7 (28.6%) | 2 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 3/12 (25%) | 3 | 0/5 (0%) | 0 |
| DEPRESSION | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| INSOMNIA | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 2/7 (28.6%) | 2 | 1/8 (12.5%) | 1 | 3/12 (25%) | 3 | 1/5 (20%) | 1 |
| NERVOUSNESS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||
| ACUTE KIDNEY INJURY | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| HAEMATURIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| PROTEINURIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| URINARY TRACT PAIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| Reproductive system and breast disorders | ||||||||||||
| VULVOVAGINAL RASH | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| COUGH | 5/7 (71.4%) | 5 | 3/9 (33.3%) | 3 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 3/12 (25%) | 4 | 2/5 (40%) | 2 |
| DYSPHONIA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| DYSPNOEA | 2/7 (28.6%) | 2 | 1/9 (11.1%) | 1 | 2/7 (28.6%) | 2 | 3/8 (37.5%) | 3 | 2/12 (16.7%) | 2 | 2/5 (40%) | 2 |
| DYSPNOEA EXERTIONAL | 2/7 (28.6%) | 2 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| EPISTAXIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 2/12 (16.7%) | 2 | 1/5 (20%) | 1 |
| HAEMOPTYSIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 2 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| HYPOXIA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| OROPHARYNGEAL PAIN | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PARANASAL SINUS HYPERSECRETION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| PNEUMOTHORAX | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PRODUCTIVE COUGH | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 2/8 (25%) | 2 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| PULMONARY EMBOLISM | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 2/12 (16.7%) | 2 | 1/5 (20%) | 1 |
| RHINORRHOEA | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| SINUS CONGESTION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| THROAT IRRITATION | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| WHEEZING | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||
| ALOPECIA | 2/7 (28.6%) | 2 | 1/9 (11.1%) | 1 | 2/7 (28.6%) | 2 | 3/8 (37.5%) | 3 | 2/12 (16.7%) | 2 | 0/5 (0%) | 0 |
| DERMATITIS | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 3 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| DRY SKIN | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| ECCHYMOSIS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| ERYTHEMA | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 2/7 (28.6%) | 2 | 1/8 (12.5%) | 1 | 1/12 (8.3%) | 2 | 0/5 (0%) | 0 |
| HYPERHIDROSIS | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| PAIN OF SKIN | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| PRURITUS | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 2/5 (40%) | 2 |
| RASH | 2/7 (28.6%) | 5 | 1/9 (11.1%) | 1 | 0/7 (0%) | 0 | 2/8 (25%) | 2 | 1/12 (8.3%) | 1 | 1/5 (20%) | 1 |
| RASH ERYTHEMATOUS | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 2 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| RASH MACULO-PAPULAR | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| RASH PAPULAR | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 1/5 (20%) | 1 |
| RASH PRURITIC | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 1/8 (12.5%) | 1 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| SKIN DISCOLOURATION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| SKIN EXFOLIATION | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
| SKIN HYPERPIGMENTATION | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/7 (0%) | 0 | 0/8 (0%) | 0 | 2/12 (16.7%) | 2 | 1/5 (20%) | 1 |
| Vascular disorders | ||||||||||||
| HOT FLUSH | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/7 (14.3%) | 1 | 0/8 (0%) | 0 | 0/12 (0%) | 0 | 0/5 (0%) | 0 |
| HYPOTENSION | 2/7 (28.6%) | 2 | 1/9 (11.1%) | 1 | 1/7 (14.3%) | 2 | 0/8 (0%) | 0 | 1/12 (8.3%) | 1 | 0/5 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT02412371
Other Study ID Numbers:
- M14-360
- 2016-001659-32
First Posted:
Apr 9, 2015
Last Update Posted:
Jul 22, 2020
Last Verified:
Jul 1, 2020