Trial Outcomes & Findings for Tiotropium + Olodaterol Fixed Dose Combination (FDC) in Chronic Obstructive Pulmonary Disease (OTEMTO 1) (NCT NCT01964352)

NCT ID: NCT01964352

Last Updated: 2015-11-25

Results Overview

Forced expiratory volume in one second (FEV1) Area under the curve (AUC) 0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in litres. FEV1 AUC0-3h response was defined as FEV1 AUC0-3h minus baseline FEV1. The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

813 participants

Primary outcome timeframe

baseline and 12 weeks

Results posted on

2015-11-25

Participant Flow

814 were entered and randomized. One patient randomized to Tiotropium 5 μg was not treated. One patient entered the study with 2 different patient numbers. This patient was counted twice in the randomized set but only once in the treated set. Thus a total of 812 unique patients were treated.

Participant milestones

Participant milestones
Measure
Placebo
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Overall Study
STARTED
204
203
202
203
Overall Study
COMPLETED
178
192
196
195
Overall Study
NOT COMPLETED
26
11
6
8

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Overall Study
Adverse Event
13
3
4
3
Overall Study
Lack of Efficacy
6
0
0
0
Overall Study
Protocol Violation
2
4
0
2
Overall Study
Lost to Follow-up
1
0
0
1
Overall Study
Withdrawal by Subject
4
2
1
0
Overall Study
Other than stated above
0
2
1
2

Baseline Characteristics

Tiotropium + Olodaterol Fixed Dose Combination (FDC) in Chronic Obstructive Pulmonary Disease (OTEMTO 1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=204 Participants
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=203 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=202 Participants
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=203 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Total
n=812 Participants
Total of all reporting groups
Age, Continuous
65.1 years
STANDARD_DEVIATION 8.3 • n=93 Participants
64.9 years
STANDARD_DEVIATION 8.2 • n=4 Participants
64.7 years
STANDARD_DEVIATION 8.2 • n=27 Participants
64.7 years
STANDARD_DEVIATION 8.9 • n=483 Participants
64.9 years
STANDARD_DEVIATION 8.4 • n=36 Participants
Sex: Female, Male
Female
77 Participants
n=93 Participants
79 Participants
n=4 Participants
86 Participants
n=27 Participants
89 Participants
n=483 Participants
331 Participants
n=36 Participants
Sex: Female, Male
Male
127 Participants
n=93 Participants
124 Participants
n=4 Participants
116 Participants
n=27 Participants
114 Participants
n=483 Participants
481 Participants
n=36 Participants

PRIMARY outcome

Timeframe: baseline and 12 weeks

Population: Patients from the Full Analysis Set (FAS): This patient set included all randomized and treated patients who had a baseline and at least one postbaseline measurement for any of the primary efficacy endpoints. The patient that entered the study with two different patient numbers was excluded from the FAS.

Forced expiratory volume in one second (FEV1) Area under the curve (AUC) 0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in litres. FEV1 AUC0-3h response was defined as FEV1 AUC0-3h minus baseline FEV1. The adjusted mean and standard error (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Outcome measures

Outcome measures
Measure
Placebo
n=204 Participants
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=203 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=202 Participants
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=202 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
FEV1 AUC0-3h Response
-0.014 L
Standard Error 0.014
0.205 L
Standard Error 0.013
0.285 L
Standard Error 0.013
0.316 L
Standard Error 0.013

PRIMARY outcome

Timeframe: baseline and 12 weeks

Population: Patients from FAS

Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FEV1 measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FEV1 response was defines as trough FEV1 minus baseline FEV1. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Outcome measures

Outcome measures
Measure
Placebo
n=198 Participants
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=200 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=201 Participants
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=200 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Trough FEV1 Response (Change From Baseline)
0.001 L
Standard Error 0.014
0.135 L
Standard Error 0.014
0.151 L
Standard Error 0.013
0.163 L
Standard Error 0.013

PRIMARY outcome

Timeframe: 12 weeks treatment

Population: Patients from FAS

This endpoint was evaluated based on the data from this individual trial and also based on the data from the combined dataset from this trial and the replicate study NCT02006732. The results for the combined dataset are included in the disclosure for NCT02006732 as specified in the analysis plan. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life). The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Outcome measures

Outcome measures
Measure
Placebo
n=186 Participants
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=192 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=199 Participants
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=196 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
St. George's Respiratory Questionnaire (SGRQ) Total Score
42.038 units on a scale
Standard Error 0.738
39.637 units on a scale
Standard Error 0.717
37.916 units on a scale
Standard Error 0.708
37.144 units on a scale
Standard Error 0.710

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Patients from FAS

Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours). It was calculated as the mean of the 2 FVC measurements performed 23 h and at 23 h 50 min after inhalation of study medication at day 85. Trough FVC response was defined as trough FVC minus baseline FVC. The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Outcome measures

Outcome measures
Measure
Placebo
n=198 Participants
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=200 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=201 Participants
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=200 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Trough Forced Vital Capacity (FVC) Response (Change From Baseline)
0.025 L
Standard Error 0.023
0.223 L
Standard Error 0.023
0.233 L
Standard Error 0.022
0.244 L
Standard Error 0.022

SECONDARY outcome

Timeframe: 12 weeks

Population: Patients from FAS

This endpoint was evaluated based on the data from this individual trial and also based on the data from the combined dataset from this trial and the replicate study NCT02006732. The results for the combined dataset are included in the disclosure for NCT02006732 as specified in the analysis plan. Mahler Transitional Dyspnoea Index (TDI) focal score was performed to measure the effect of the treatment on patients' dyspnoea.(Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9). The adjusted mean (SE) are obtained from fitting an MMRM model including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Outcome measures

Outcome measures
Measure
Placebo
n=187 Participants
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=193 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=199 Participants
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=196 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
TDI Focal Score
-0.113 Units on a scale
Standard Error 0.196
1.332 Units on a scale
Standard Error 0.192
1.839 Units on a scale
Standard Error 0.189
1.939 Units on a scale
Standard Error 0.190

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Patients from FAS

The adjusted mean (SE) are obtained from fitting a mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment by test day interaction, baseline, and baseline by test day interaction; patient as a random effect; spatial power covariance structure for within-patient errors and Kenward-Roger approximation of denominator degrees of freedom.

Outcome measures

Outcome measures
Measure
Placebo
n=204 Participants
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=203 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=202 Participants
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=202 Participants
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
FVC AUC0-3h Response (Change From Baseline)
-0.011 L
Standard Error 0.025
0.286 L
Standard Error 0.024
0.387 L
Standard Error 0.023
0.446 L
Standard Error 0.023

Adverse Events

Placebo

Serious events: 11 serious events
Other events: 32 other events
Deaths: 0 deaths

Tiotropium 5 μg

Serious events: 6 serious events
Other events: 28 other events
Deaths: 0 deaths

Tiotropium 2.5 μg+ Olodaterol 5 μg

Serious events: 4 serious events
Other events: 25 other events
Deaths: 0 deaths

Tiotropium 5 μg + Olodaterol 5 μg

Serious events: 10 serious events
Other events: 16 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=204 participants at risk
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=203 participants at risk
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=202 participants at risk
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=203 participants at risk
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Cardiac disorders
Angina unstable
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Cardiac disorders
Atrial fibrillation
0.98%
2/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Cardiac disorders
Cardiac failure
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Cardiac disorders
Cardiomyopathy
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Cardiac disorders
Ischaemic cardiomyopathy
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Cardiac disorders
Myocardial infarction
0.00%
0/204 • up to 112 days
0.49%
1/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Gastrointestinal disorders
Colitis
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
General disorders
Chest pain
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Hepatobiliary disorders
Autoimmune hepatitis
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Infections and infestations
Cellulitis
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.50%
1/202 • up to 112 days
0.00%
0/203 • up to 112 days
Infections and infestations
Erysipelas
0.00%
0/204 • up to 112 days
0.49%
1/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Infections and infestations
Gangrene
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.50%
1/202 • up to 112 days
0.00%
0/203 • up to 112 days
Infections and infestations
Gastrointestinal bacterial infection
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Infections and infestations
Localised infection
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.50%
1/202 • up to 112 days
0.00%
0/203 • up to 112 days
Infections and infestations
Pneumonia
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Infections and infestations
Pneumonia bacterial
0.00%
0/204 • up to 112 days
0.49%
1/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Infections and infestations
Sinusitis
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Infections and infestations
Viral infection
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Injury, poisoning and procedural complications
Accidental overdose
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.50%
1/202 • up to 112 days
0.00%
0/203 • up to 112 days
Injury, poisoning and procedural complications
Cervical vertebral fracture
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Injury, poisoning and procedural complications
Clavicle fracture
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.50%
1/202 • up to 112 days
0.00%
0/203 • up to 112 days
Injury, poisoning and procedural complications
Road traffic accident
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Musculoskeletal and connective tissue disorders
Osteoarthritis
0.98%
2/204 • up to 112 days
0.49%
1/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm of unknown primary site
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Nervous system disorders
Cerebrovascular accident
0.00%
0/204 • up to 112 days
0.49%
1/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Nervous system disorders
Convulsion
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Nervous system disorders
Lumbar radiculopathy
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Psychiatric disorders
Acute stress disorder
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Psychiatric disorders
Bipolar disorder
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Psychiatric disorders
Depression
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Psychiatric disorders
Suicide attempt
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
1.5%
3/204 • up to 112 days
0.49%
1/203 • up to 112 days
0.50%
1/202 • up to 112 days
0.49%
1/203 • up to 112 days
Respiratory, thoracic and mediastinal disorders
Pneumothorax
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.49%
1/203 • up to 112 days
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
0.00%
0/204 • up to 112 days
0.49%
1/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Respiratory, thoracic and mediastinal disorders
Respiratory failure
0.49%
1/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.00%
0/202 • up to 112 days
0.00%
0/203 • up to 112 days
Vascular disorders
Peripheral ischaemia
0.00%
0/204 • up to 112 days
0.00%
0/203 • up to 112 days
0.50%
1/202 • up to 112 days
0.00%
0/203 • up to 112 days

Other adverse events

Other adverse events
Measure
Placebo
n=204 participants at risk
Once daily 2 puffs solution of placebo for inhalation with Respimat
Tiotropium 5 μg
n=203 participants at risk
Once daily 2 puffs solution of 2.5 μg tiotropium for inhalation with Respimat
Tiotropium 2.5 μg+ Olodaterol 5 μg
n=202 participants at risk
Once daily 2 puffs solution of 1.25 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Tiotropium 5 μg + Olodaterol 5 μg
n=203 participants at risk
Once daily 2 puffs solution of 2.5 μg tiotropium / 2.5 μg olodaterol for inhalation with Respimat.
Infections and infestations
Nasopharyngitis
5.9%
12/204 • up to 112 days
4.4%
9/203 • up to 112 days
4.5%
9/202 • up to 112 days
3.4%
7/203 • up to 112 days
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
9.8%
20/204 • up to 112 days
9.4%
19/203 • up to 112 days
7.9%
16/202 • up to 112 days
4.4%
9/203 • up to 112 days

Additional Information

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Phone: 1-800-243-0127

Results disclosure agreements

  • Principal investigator is a sponsor employee Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
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Restriction type: OTHER