Trial Outcomes & Findings for Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection (NCT NCT00952822)

NCT ID: NCT00952822

Last Updated: 2021-05-24

Results Overview

Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 52 participants
• Primary outcome timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
• Results posted on: 2021-05-24

Participant Flow

Enrollment was conducted in the United States at 11 sites. Two cohorts were recruited (adolescent/adults aged ≥12 to ≤65 years and pediatrics aged ≥2 to <12 years).

Subjects meeting inclusion criteria were randomly assigned to receive a single sequence of 2 pharmacokinetic (PK) infusions of rAHF-PFM: reconstituted in 2mL then 5mL sterile water for injection (SWFI) or vice versa. Before each PK evaluation ≥3 day washout and negative factor VIII inhibitor titer was required. Ten subjects were screen failures

Participant milestones

Measure	Adolescents/Adults - 2 mL Then 5 mL Adolescents/Adults - 2 mL then 5 mL: Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 5 mL SWFI for the 2nd PK Evaluation.	Adolescents/Adults - 5 mL Then 2 mL Adolescents/Adults - 5 mL then 2 mL: Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 2 mL SWFI for the 2nd PK Evaluation.	Pediatrics - 2 mL Then 5 mL Pediatrics - 2 mL then 5 mL: Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 5 mL SWFI for the 2nd PK Evaluation.	Pediatrics - 5 mL Then 2 mL Pediatrics - 5 mL then 2 mL: Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 2 mL SWFI for the 2nd PK Evaluation.
1st Pharmacokinetic Evaluation STARTED	9	18	11	4
1st Pharmacokinetic Evaluation COMPLETED	9	17	11	4
1st Pharmacokinetic Evaluation NOT COMPLETED	0	1	0	0
2nd Pharmacokinetic Evaluation STARTED	9	17	11	4
2nd Pharmacokinetic Evaluation COMPLETED	9	17	10	4
2nd Pharmacokinetic Evaluation NOT COMPLETED	0	0	1	0

Reasons for withdrawal

Measure	Adolescents/Adults - 2 mL Then 5 mL Adolescents/Adults - 2 mL then 5 mL: Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 5 mL SWFI for the 2nd PK Evaluation.	Adolescents/Adults - 5 mL Then 2 mL Adolescents/Adults - 5 mL then 2 mL: Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 2 mL SWFI for the 2nd PK Evaluation.	Pediatrics - 2 mL Then 5 mL Pediatrics - 2 mL then 5 mL: Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 5 mL SWFI for the 2nd PK Evaluation.	Pediatrics - 5 mL Then 2 mL Pediatrics - 5 mL then 2 mL: Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI for the 1st Pharmacokinetic (PK) Evaluation, then rAHF-PFM reconstituted in 2 mL SWFI for the 2nd PK Evaluation.
1st Pharmacokinetic Evaluation Lost to Follow-up	0	1	0	0
2nd Pharmacokinetic Evaluation Withdrawal by Subject	0	0	1	0

Baseline Characteristics

Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection

Baseline characteristics by cohort

Measure	Treated Participants n=42 Participants Participants who received at least 1 infusion
Age, Continuous Pediatrics	6 years STANDARD_DEVIATION 3 • n=5 Participants
Age, Continuous Adolescents/Adults	26 years STANDARD_DEVIATION 10 • n=5 Participants
Age, Customized ≥2 to <12 years (Number Pediatrics)	15 Participants n=5 Participants
Age, Customized ≥12 to <16 years (Number Adolescents)	3 Participants n=5 Participants
Age, Customized ≥16 to 65 years (Number Adults)	24 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Region of Enrollment United States	42 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Population: Number of complete crossover participants (per protocol) who received the assigned sequence of 2 infusions: reconstituted in 2mL then 5mL SWFI or in 5mL then 2mL SWFI.

Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method

Outcome measures

Measure	Adolescents/Adults - 2 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Area Under the Curve	1257.20 IU*h/dL Standard Deviation 380.60	1297.42 IU*h/dL Standard Deviation 487.57	—	—

SECONDARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Population: Number of complete crossover participants (intent to treat) who received the assigned sequence of 2 infusions: reconstituted in 2mL then 5mL SWFI or in 5mL then 2mL SWFI.

Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model

Outcome measures

Measure	Adolescents/Adults - 2 mL n=25 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=25 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Total Area Under the Curve	1357.60 IU*h/dL Standard Deviation 436.24	1368.12 IU*h/dL Standard Deviation 553.21	—	—

SECONDARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion

Population: Intent to Treat

Increase in factor VIII concentration from pre- to post-infusion

Outcome measures

Measure	Adolescents/Adults - 2 mL n=26 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=26 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL n=15 Participants Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL n=14 Participants Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Adjusted in Vivo Incremental Recovery	1.87 IU/dL:IU/kg Standard Deviation 0.34	1.88 IU/dL:IU/kg Standard Deviation 0.40	1.33 IU/dL:IU/kg Standard Deviation 0.36	1.66 IU/dL:IU/kg Standard Deviation 0.25

SECONDARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Population: Per Protocol

Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.

Outcome measures

Measure	Adolescents/Adults - 2 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Terminal Half-life	12.54 hours Standard Deviation 3.80	12.50 hours Standard Deviation 2.89	—	—

SECONDARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Population: Per Protocol

Computed as the weight-adjusted dose divided by total AUC

Outcome measures

Measure	Adolescents/Adults - 2 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Weight-Adjusted Clearance	3.85 mL/(kg*h) Standard Deviation 0.95	3.81 mL/(kg*h) Standard Deviation 1.20	—	—

SECONDARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Population: Per Protocol

Computed as total area under the moment curve divided by the total AUC. Total area under the first moment curve (AUMC) estimated by linear trapezoidal methods

Outcome measures

Measure	Adolescents/Adults - 2 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Mean Residence Time	14.79 hours (h) Standard Deviation 5.24	14.34 hours (h) Standard Deviation 4.27	—	—

SECONDARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Population: Per Protocol

Computed as weight-adjusted clearance * mean residence time

Outcome measures

Measure	Adolescents/Adults - 2 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Volume of Distribution at Steady State	0.54 dL/kg Standard Deviation 0.13	0.51 dL/kg Standard Deviation 0.13	—	—

SECONDARY outcome

Timeframe: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion

Population: Per Protocol

Maximal factor VIII concentration post-infusion

Outcome measures

Measure	Adolescents/Adults - 2 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=19 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Maximum Plasma Concentration	102.77 IU/dL Standard Deviation 19.35	106.46 IU/dL Standard Deviation 17.95	—	—

SECONDARY outcome

Timeframe: Within 5 minutes pre-infusion up to 24 hours post-infusion

Population: Participants who received at least 1 infusion

Infusion-related local reactions (including pain, tenderness, erythema, induration, and bruising) and severity were evaluated according to an FDA-defined grading scale (FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; 2007).

Outcome measures

Measure	Adolescents/Adults - 2 mL n=27 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=27 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL n=15 Participants Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL n=15 Participants Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Number and Severity of Infusion Site Reactions Erythema- Mild (Grade 1)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Erythema- Moderate (Grade 2)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Pain- Moderate (Grade 2)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Pain- Severe (Grade 3)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Erythema- Severe (Grade 3)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Tenderness- Severe (Grade 3)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Pain- Mild (Grade 1)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Tenderness- Potentially Life Threatening (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Pain- Potentially Life Threatening (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Tenderness- Mild (Grade 1)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Tenderness- Moderate (Grade 2)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Erythema- Potentially Life Threatening (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Induration- Mild (Grade 1)	0 Participants	0 Participants	1 Participants	0 Participants
Number and Severity of Infusion Site Reactions Induration- Moderate (Grade 2)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Induration- Severe (Grade 3)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Induration- Potentially Life Threatening (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Bruising- Mild (Grade 1)	0 Participants	0 Participants	1 Participants	0 Participants
Number and Severity of Infusion Site Reactions Bruising- Moderate (Grade 2)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Bruising- Severe (Grade 3)	0 Participants	0 Participants	0 Participants	0 Participants
Number and Severity of Infusion Site Reactions Bruising- Potentially Life Threatening (Grade 4)	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Within 5 minutes post-infusion up to 24 hours post-infusion

Population: Participants who received at least 1 infusion

Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).

Outcome measures

Measure	Adolescents/Adults - 2 mL n=26 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 2 mL SWFI	Adolescents/Adults - 5 mL n=27 Participants Participants aged ≥12 to ≤65 years who received rAHF-PFM reconstituted in 5 mL SWFI	Pediatrics - 2 mL n=8 Participants Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 2 mL SWFI	Pediatrics - 5 mL n=8 Participants Participants aged ≥2 to \<12 years who received rAHF-PFM reconstituted in 5 mL SWFI
Infusion Site Pain Within 5 minutes (immediately) after infusion	0 Scores on a scale Interval 0.0 to 12.0	0 Scores on a scale Interval 0.0 to 27.0	8 Scores on a scale Interval 0.0 to 37.0	4 Scores on a scale Interval 0.0 to 61.0
Infusion Site Pain 60 ± 5 minutes after infusion	0 Scores on a scale Interval 0.0 to 3.0	0 Scores on a scale Interval 0.0 to 4.0	2.5 Scores on a scale Interval 0.0 to 66.0	1 Scores on a scale Interval 0.0 to 7.0
Infusion Site Pain 6 hours ± 30 minutes after infusion	0 Scores on a scale Interval 0.0 to 3.0	0 Scores on a scale Interval 0.0 to 2.0	0 Scores on a scale Interval 0.0 to 8.0	0 Scores on a scale Interval 0.0 to 4.0
Infusion Site Pain 24 hours after infusion	0 Scores on a scale Interval 0.0 to 2.0	0 Scores on a scale Interval 0.0 to 3.0	0 Scores on a scale Interval 0.0 to 8.0	0 Scores on a scale Interval 0.0 to 2.0

Adverse Events

Adolescents/Adults

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Pediatrics

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Adolescents/Adults n=27 participants at risk Participants aged ≥12 to ≤65 years who received at least one infusion	Pediatrics n=15 participants at risk Participants aged ≥12 to ≤65 years who received at least one infusion
General disorders Pyrexia	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits

Other adverse events

Measure	Adolescents/Adults n=27 participants at risk Participants aged ≥12 to ≤65 years who received at least one infusion	Pediatrics n=15 participants at risk Participants aged ≥12 to ≤65 years who received at least one infusion
Immune system disorders Allergy to arthropod sting	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
Injury, poisoning and procedural complications Arthropod bite	3.7% 1/27 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	13.3% 2/15 • Number of events 2 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
General disorders Catheter thrombosis	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
Eye disorders Conjunctival hemorrhage	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
Injury, poisoning and procedural complications Contusion	3.7% 1/27 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	33.3% 5/15 • Number of events 5 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
Infections and infestations Ear infection	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
Musculoskeletal and connective tissue disorders Hemarthrosis	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
General disorders Injection site hematoma	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
General disorders Injection site swelling	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits
Musculoskeletal and connective tissue disorders Joint range of motion	0.00% 0/27 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits	6.7% 1/15 • Number of events 1 • During course of study AEs were collected by the investigators at study visits, and may result from laboratory and vital sign assessments collected or measured at the study visits

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee Baxter's agreements with PIs vary per individual PI, but contain common elements. For this study, PIs are restricted from independently publishing results until the earlier of the primary multicenter publication or 1 year after study completion. Baxter requires a review of results communications (e.g., for confidential information) up to 90 days prior to submission or communication. Baxter may request an additional delay of up to 60 days (e.g., to allow for intellectual property protection).
• Publication restrictions are in place

Restriction type: OTHER