Trial Outcomes & Findings for A Study of Varenicline for Prevention of Relapse to Smoking in Patients With Schizophrenia or Bipolar Disorder (NCT NCT00621777)

NCT ID: NCT00621777

Last Updated: 2017-12-21

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

247 participants

Primary outcome timeframe

76 weeks

Results posted on

2017-12-21

Participant Flow

Enrolled from 03/08 to 04/12 from 10 community mental health centers in MA, MI, NH, IN, AL, and MN, participants were 18-70 years, outpatients with schizophrenia, schizoaffective or bipolar disorder, smoked 10+ cigs/day, had CO levels \>9 ppm, willing to take varenicline, agreed to set a quit date within 4 wks of enrollment, and were stable

44 participants were excluded after signing consent: 4 site closure, 40 Did not meet inclusion criteria, 17 Active substance abuse, 8 Unstable medical condition, 8 Unstable psychological symptoms, 4 Lost to follow-up, 3 Other

Participant milestones

Participant milestones
Measure	Varenicline Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. 1. Open label, smoking cessation phase: At each weekly study visit from the baseline visit to study wk 11, ALL subjects will receive a one-week supply of varenicline as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 wks. 2. Double-Blind, Placebo-Controlled, Relapse-Prevention Phase: Participants in the open phase who met criteria for biochemically verified, 7-day, point-prevalence abstinence at wks 11 and 12 were considered to be continuously abstinent for at least 14 days and were randomized to continue varenicline, 1.0 mg twice a day, or switch to identical-appearing placebo for wks 12 through 52	Placebo Placebo: At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.
Open Phase STARTED	203	0
Open Phase COMPLETED	87	0
Open Phase NOT COMPLETED	116	0
Randomized Phase STARTED	40	47
Randomized Phase COMPLETED	33	28
Randomized Phase NOT COMPLETED	7	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Varenicline Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. 1. Open label, smoking cessation phase: At each weekly study visit from the baseline visit to study wk 11, ALL subjects will receive a one-week supply of varenicline as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 wks. 2. Double-Blind, Placebo-Controlled, Relapse-Prevention Phase: Participants in the open phase who met criteria for biochemically verified, 7-day, point-prevalence abstinence at wks 11 and 12 were considered to be continuously abstinent for at least 14 days and were randomized to continue varenicline, 1.0 mg twice a day, or switch to identical-appearing placebo for wks 12 through 52	Placebo Placebo: At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.
Open Phase Adverse Event	20	0
Open Phase Did not abstain during open phase	56	0
Open Phase Withdrawal by Subject	17	0
Open Phase administrative	13	0
Open Phase Lost to Follow-up	10	0
Randomized Phase Adverse Event	3	3
Randomized Phase Lost to Follow-up	3	3
Randomized Phase Withdrawal by Subject	1	9
Randomized Phase administrative	0	3
Randomized Phase Death	0	1

Baseline Characteristics

A Study of Varenicline for Prevention of Relapse to Smoking in Patients With Schizophrenia or Bipolar Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Varenicline n=40 Participants Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. Varenicline has demonstrated safety when dosed at 1 mg twice per day for up to one year. Varenicline: At each weekly study visit from the baseline visit to study week 11, ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the varenicline condition will receive varenicline at the dose used to attain initial abstinence for 40 weeks.	Placebo n=47 Participants Placebo: At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.	Total n=87 Participants Total of all reporting groups
Age, Continuous	51.4 years STANDARD_DEVIATION 9.6 • n=5 Participants	45.7 years STANDARD_DEVIATION 10.3 • n=7 Participants	47.5 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	31 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	34 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	7 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=5 Participants	47 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 76 weeks

Outcome measures

Outcome measures
Measure	Varenicline n=40 Participants Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. Varenicline has demonstrated safety when dosed at 1 mg twice per day for up to one year. Varenicline: At each weekly study visit from the baseline visit to study week 11, ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the varenicline condition will receive varenicline at the dose used to attain initial abstinence for 40 weeks.	Placebo n=47 Participants Placebo: At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.
Rate of 7-day Point Prevalence Abstinence at the End of the Relapse Prevention Phase (Study Week 53) in the Extended Duration Pharmacotherapy Group vs. the Placebo Group 7-day, point-prevalence abstinence at week 52	24 participants	9 participants
Rate of 7-day Point Prevalence Abstinence at the End of the Relapse Prevention Phase (Study Week 53) in the Extended Duration Pharmacotherapy Group vs. the Placebo Group Continuous abstinence, weeks 12-64	18 participants	7 participants
Rate of 7-day Point Prevalence Abstinence at the End of the Relapse Prevention Phase (Study Week 53) in the Extended Duration Pharmacotherapy Group vs. the Placebo Group Continuous abstinence, weeks 12-76	12 participants	5 participants

SECONDARY outcome

Timeframe: at week 52

Population: Only 63 subjects completed study visit #52, therefore only these subjects were analyzed at this time point for this variable

Brief Psychiatric Rating Scale is a 24 item scale that is designed to assess positive and negative symptoms, and general psychopathology in people with serious mental illness. Each item is rated on a 7-point scale from not present to extremely severe; higher scores in a range of 24 to 168, indicate more severe symptoms Ratings are based on observation and patient report. The validity of the BPRS is generally high when compared with other measures of general psychopathology. It was administered at baseline, study weeks 12, 18, 26, 38, 52

Outcome measures

Outcome measures
Measure	Varenicline n=31 Participants Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. Varenicline has demonstrated safety when dosed at 1 mg twice per day for up to one year. Varenicline: At each weekly study visit from the baseline visit to study week 11, ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the varenicline condition will receive varenicline at the dose used to attain initial abstinence for 40 weeks.	Placebo n=32 Participants Placebo: At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.
Safety and Tolerability of Extended Duration Pharmacotherapy When Added to Antipsychotic Medications in Schizophrenia Patients Who Have Recently Quit Smoking as Assessed by the Brief Psychiatric Rating Scale	50.43 units on a scale Standard Deviation 15.08	47.88 units on a scale Standard Deviation 12.12

SECONDARY outcome

Timeframe: at week 52

The 12-Item Short Form Health Survey (SF-12) is a 12-item measure of perceived health status with good reliability, validity and correlation with other health measures. It is scored via a standard algorithm, with higher scores indicating better patient self perception of health, with a mean score of 50 and a standard deviation of 10 in a representative sample of the US population. The score is computed using the scores of the twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health and 100 indicates the highest level of health. This was administered at baseline and end of study.

Outcome measures

Outcome measures
Measure	Varenicline n=30 Participants Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. Varenicline has demonstrated safety when dosed at 1 mg twice per day for up to one year. Varenicline: At each weekly study visit from the baseline visit to study week 11, ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the varenicline condition will receive varenicline at the dose used to attain initial abstinence for 40 weeks.	Placebo n=30 Participants Placebo: At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks. In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.
Effect of Treatment With Varenicline Versus Placebo on Health-related Quality of Life Indices in Recently Abstinent Smokers With Schizophrenia or Bipolar Disorder as Measured by the 12-Item Short Form Health Survey (SF-12)	47.59 units on a scale Standard Deviation 10.95	48.39 units on a scale Standard Deviation 9.05

Adverse Events

Varenicline Open Label (Open Phase)

Serious events: 3 serious events

Other events: 113 other events

Deaths: 0 deaths

Varenicline

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Varenicline Open Label (Open Phase) n=203 participants at risk Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. 1\. Open label, smoking cessation phase: At each weekly study visit from the baseline visit to study wk 11, ALL subjects will receive a one-week supply of varenicline as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 wks.	Varenicline n=40 participants at risk Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. 2\. Double-Blind, Placebo-Controlled, Relapse-Prevention Phase: Participants in the open phase who met criteria for biochemically verified, 7-day, point-prevalence abstinence at wks 11 and 12 were considered to be continuously abstinent for at least 14 days and were randomized to continue varenicline, 1.0 mg twice a day, or switch to identical-appearing placebo for wks 12 through 52	Placebo n=47 participants at risk 2\. Double-Blind, Placebo-Controlled, Relapse-Prevention Phase: Participants in the open phase who met criteria for biochemically verified, 7-day, point-prevalence abstinence at wks 11 and 12 were considered to be continuously abstinent for at least 14 days and were randomized to continue varenicline, 1.0 mg twice a day, or switch to identical-appearing placebo for wks 12 through 52
Metabolism and nutrition disorders Sepsis associated with complications of diabetes that resulted in death	0.00% 0/203 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	0.00% 0/40 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	2.1% 1/47 • Number of events 1 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.
Cardiac disorders Myocardial infarction	0.00% 0/203 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	0.00% 0/40 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	2.1% 1/47 • Number of events 1 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.
Metabolism and nutrition disorders Pancreatitis	0.00% 0/203 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	2.5% 1/40 • Number of events 1 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	0.00% 0/47 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/203 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	2.5% 1/40 • Number of events 1 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	0.00% 0/47 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.
Psychiatric disorders psychiatric hospitalization	1.5% 3/203 • Number of events 3 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	5.0% 2/40 • Number of events 2 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.	10.6% 5/47 • Number of events 5 • At every visit: Calgary Depression Scale, the Montgomery-Asberg Depression and the Young Mania Rating Scales. AEs were ascertained by general/specific query: headache, nausea, vomiting, tachycardia, excitement, agitation, anxiety, insomnia, irritability. Additional assessments were conducted at baseline; at study weeks 12, 18, 26, 38, 52, and 64; the Brief Psychiatric Rating Scale, Schedule for the Assessment of Negative Symptoms and assessments for health-related quality of life were conducted at baseline and weeks 12, 52, and 64.

Other adverse events

Additional Information

A. Eden Evins, MD, MPH

Massachusetts General Hospital

Phone: 6176434679

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place