Trial Outcomes & Findings for Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer (NCT NCT02673398)

Last Updated: 2023-06-18

Results Overview

Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tables will be created to summarize the toxicities and side effects by organ system, attribution and severity for all participants that receive at least one dose of neratinib. Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for grade 2 or higher toxicities attributed to neratinib.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

On treatment, 28 days per cycle up to 1 year

Results posted on

2023-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Neratinib) Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Overall Study STARTED	25
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Age, Continuous	66 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants
ECOG performance status 0 = Fully active, able to carry on all pre-disease performance without restriction	8 Participants n=5 Participants
ECOG performance status 1 = Restricted in physically strenuous activity but ambulatory and able to do work of a light nature	17 Participants n=5 Participants
Hormone receptor status Positive	19 Participants n=5 Participants
Hormone receptor status Negative	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: On treatment, 28 days per cycle up to 1 year

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Percent of Participants With Grade 2 or Higher Toxicities	80 percentage of participants Interval 59.0 to 93.0

SECONDARY outcome

Timeframe: On treatment, 28 days per cycle up to 1 year

Will be graded according to the NCI CTCAE version 4.0. Tables will be created to summarize the toxicities and side effects by organ system, attribution and severity for all participants that receive at least one dose of neratinib.

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Count of Participants With Grade 3 or Higher Gastrointestinal (GI) Toxicities Such as Diarrhea, Nausea and Vomiting Diarrhea	5 Participants
Count of Participants With Grade 3 or Higher Gastrointestinal (GI) Toxicities Such as Diarrhea, Nausea and Vomiting Vomiting	2 Participants
Count of Participants With Grade 3 or Higher Gastrointestinal (GI) Toxicities Such as Diarrhea, Nausea and Vomiting Abdominal pain	2 Participants
Count of Participants With Grade 3 or Higher Gastrointestinal (GI) Toxicities Such as Diarrhea, Nausea and Vomiting Nausea	1 Participants

SECONDARY outcome

Timeframe: On treatment, up to 48 months

Population: 9 of 25 patients 36% had a dose reduction.

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for dose reduction.

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Rate of Participants With a Dose Reduction	36 percentage of participants Interval 18.0 to 57.0

SECONDARY outcome

Timeframe: On treatment, up to 48 months

Population: 4 of 25 patients (16%) were hospitalized.

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for hospitalizations.

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Rate of Participants Requiring Hospitalizations	16 percentage of participants Interval 5.0 to 36.0

SECONDARY outcome

Timeframe: Participants are evaluated every 12 weeks, up to 48 months

Complete Response (CR): Disappearance of all target lesions. Lymph node CR is when the lymph node has decreased to less than 10mm in the short axis. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started (including the baseline scan if that is the smallest), and at least a 5mm increase or the appearance of new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Partial Remission	1 Participants
Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Stable Disease	11 Participants
Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Progressive Disease	12 Participants
Tumor Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Not assessed	1 Participants

SECONDARY outcome

Timeframe: From the date treatment begins until the first date on which recurrence, progression or death due to any cause, assessed up to 48 months

Rates and associated 95% exact Clopper and Pearson binomial confidence limits will be estimated for PFS. PFS will be estimated using the product limit method of Kaplan and Meier.

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Median Progression-free Survival (PFS) in Months	2.6 months Interval 2.56 to 5.26

SECONDARY outcome

Timeframe: Time from start of treatment to death due to any cause, assessed up to 48 months

OS will be estimated using the product limit method of Kaplan and Meier.

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=25 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Median Overall Survival (OS)	17.4 months Interval 10.3 to insufficient number of participants with events

SECONDARY outcome

Timeframe: At day 0 of treatment

Population: 3 participants did not have complete geriatric assessment data.

The cancer specific geriatric assessment score includes an evaluation of functional status, co-morbidity, cognition, psychological stats, social functioning and support, and nutritional status. It assesses a patient's age, gender, height, weight, cancer type, dosage, number of chemotherapy agents, hemoglobin, hearing, number of falls in past 6 months, able to take own medicine, whether walking is limited, have physical or emotional problems interfered with social activities and serum creatinine. Scores can range from 0 to to 1, with a higher score indicating higher risk of chemotherapy toxicity. Generalized linear models and graphical methods will be used to explore factors as identified by a cancer-specific geriatric assessment.

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=22 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Cancer-specific Geriatric Assessment Score	0.34 scores on a scale Interval 0.19 to 0.59

SECONDARY outcome

Timeframe: Day 0 to day 15

Population: Only 20 participants had PK data available.

Least squares regression was used to assess the relationship between steady state neratinib concentration, transformed using a logarithm base 2 transformation, and age

Outcome measures

Outcome measures
Measure	Treatment (Neratinib) n=20 Participants Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Pharmacokinetics of Steady State Neratinib Concentration Transformed Using a Logarithm Base 2	4.7 log2(ng/mL) Standard Deviation 1.09

Adverse Events

Treatment (Neratinib)

Serious events: 10 serious events

Other events: 23 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Neratinib) n=25 participants at risk Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Respiratory, thoracic and mediastinal disorders Dyspnea	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Cardiac disorders Pericardial tampo	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Abdominal pain	8.0% 2/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Diarrhea	8.0% 2/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Nausea	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Vomiting	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Infections and infestations Appendicitis	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Investigations Weight loss	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Metabolism and nutrition disorders Dehydration	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Musculoskeletal and connective tissue disorders T7 mets with spinal cord compression	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
General disorders Death	24.0% 6/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Respiratory, thoracic and mediastinal disorders Hypoxemic respiratory failure	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Respiratory, thoracic and mediastinal disorders Pneumonia	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).

Other adverse events

Other adverse events
Measure	Treatment (Neratinib) n=25 participants at risk Patients receive neratinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Comprehensive Geriatric Assessment: Ancillary studies Laboratory Biomarker Analysis: Correlative studies Neratinib: Given PO Pharmacological Study: Correlative studies
Blood and lymphatic system disorders Anemia	16.0% 4/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Blood and lymphatic system disorders Lymphocyte count decreased	24.0% 6/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Blood and lymphatic system disorders White blood cell count decreased	16.0% 4/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Abdominal pain	12.0% 3/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Diarrhea	60.0% 15/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Nausea	12.0% 3/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Gastrointestinal disorders Vomiting	8.0% 2/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
General disorders Anorexia	12.0% 3/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
General disorders Dehydration	8.0% 2/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
General disorders Fatigue	12.0% 3/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
General disorders Generalized muscle weakness	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
General disorders Weight loss	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Investigations Acute kidney injury	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Investigations Aspartate aminotransferase increased	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Investigations Creatinine increased	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Skin and subcutaneous tissue disorders Rash maculo-papular	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Skin and subcutaneous tissue disorders Skin laceration	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Cardiac disorders Ejection fraction decreased	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Cardiac disorders Hypertension	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Cardiac disorders Syncope	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Blood and lymphatic system disorders Neutrophil count decreased	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Blood and lymphatic system disorders Platelet count decreased	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).
Investigations Hypoalbuminemia	4.0% 1/25 • Through study completion, an average of 18 months All serious adverse events are reported regardless of attribution and grade. Count of participants experiencing grade 2, 3, 4, or 5 other adverse events possibly, probably, or definitely attributed to neratinib are reported (after removing serious adverse events from the toxicity dataset).

Additional Information

Dr. Yuan Yuan

City of Hope

Phone: 626-359-8111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place