Trial Outcomes & Findings for Comparison of Pharmacokinetic, Safety, Tolerability of Alpha-1 MP and Prolastin In Alpha1-antitrypsin Deficient Adults (NCT NCT00295061)

Last Updated: 2014-09-09

Results Overview

The primary objective of this study was to demonstrate the pharmacokinetic comparability (geometric least square mean ratio of AUC between the Alpha-1 MP vs. Prolastin®, 90% confidence interval falls within 0.80-1.25, FDA Guidance as being "bioequivalent" between two treatments) of Alpha-1 MP to Prolastin® in subjects with alpha-1-anti-trypsin (AAT) deficiency by comparing AUC from Day 0 to Day 7 of plasma Alpha1-PI measured by the functional activity (potency) assay. AUC from Day 0 to Day 7 was calculated at steady state at the end of the first and second 8-week treatment periods during the 16-week double-blind, crossover phase.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

24 participants

Primary outcome timeframe

Day 0 to Day 7

Results posted on

2014-09-09

Participant Flow

First-subject-first-dose was on 22 May 2006, Last-subject-last-visit was on 28 Feb 2007. The trial was performed at 6 clinical sites in the United States.

Participant milestones

Participant milestones
Measure	Alpha-1 MP / Prolastin Sequential, blinded treatment periods of Alpha-1 modified process (MP) (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP	Prolastin / Alpha-1 MP Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP
Overall Study STARTED	12	12
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Comparison of Pharmacokinetic, Safety, Tolerability of Alpha-1 MP and Prolastin In Alpha1-antitrypsin Deficient Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alpha-1 MP / Prolastin n=12 Participants Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP	Prolastin / Alpha-1 MP n=12 Participants Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	58.4 years STANDARD_DEVIATION 6.86 • n=5 Participants	57.0 years STANDARD_DEVIATION 9.33 • n=7 Participants	57.7 years STANDARD_DEVIATION 8.04 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 to Day 7

Outcome measures

Outcome measures
Measure	Alpha-1 MP n=24 Participants Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP	Prolastin n=24 Participants Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP
Alpha-1 MP vs. Prolastin® of Area Under the Curve (AUC) From Day 0 to Day 7	155.9 mg*h/mL Interval 0.97 to 1.09	152.4 mg*h/mL Interval 0.97 to 1.09

Adverse Events

Alpha-1 MP

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Prolastin

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alpha-1 MP n=24 participants at risk Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP	Prolastin n=24 participants at risk Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.00% 0/24	4.2% 1/24 • Number of events 1
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/24	4.2% 1/24 • Number of events 1

Other adverse events

Other adverse events
Measure	Alpha-1 MP n=24 participants at risk Sequential, blinded treatment periods of Alpha-1 MP (experimental), then crossed-over to Prolastin (active comparator), followed by open-label Alpha-1 MP	Prolastin n=24 participants at risk Sequential, blinded treatment periods of Prolastin (active comparator), then crossed-over to Alpha-1 MP (experimental), followed by open-label Alpha-1 MP
Infections and infestations Upper respiratory tract infection	8.3% 2/24 • Number of events 2	4.2% 1/24 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/24	8.3% 2/24 • Number of events 2
Nervous system disorders Headache	4.2% 1/24 • Number of events 1	8.3% 2/24 • Number of events 3

Additional Information

Henry Li

Grifols Therapeutics

Phone: 1-800-520-2807

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator must send a draft manuscript of the publication or abstract to the sponsor thirty days in advance of submission in order to obtain approval prior to submission of the final version for publication. This will be reviewed promptly and approval will not be withheld unreasonably. In case of a difference of opinion between the sponsor and the investigator(s), the contents of the publication will be discussed in order to find a solution which satisfies both parties.
Publication restrictions are in place

Restriction type: OTHER