SOLUTION: Study of Oral Liprotamase Unit-Matched Therapy Of Non-Porcine Origin in Patients With Cystic Fibrosis

• Sponsor: Anthera Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02279498
• Collaborator: (none)
• Enrollment: 128
• Locations: 54
• Arms: 2
• Actual Duration (Months): 19.7
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Liprotamase powder is a non-porcine, soluble and stable mixture of three digestive enzymes including lipase, protease, and amylase. The purpose of the present study is to provide additional efficacy and safety data compared to approved, porcine-derived, enterically-coated and encapsulated pancreatic enzyme replacement therapy. The primary efficacy endpoint of the study will be comparative efficacy measured as the change in the coefficient of fat absorption (CFA) in Cystic Fibrosis patients with exocrine pancreatic insufficiency (EPI).

Liprotamase is stable in stomach and digestive fluids allowing administration in a variety of convenient formulations and with a number of foods without enteric coating.

Condition or Disease	Intervention/Treatment	Phase
Exocrine Pancreatic Insufficiency; Cystic Fibrosis	Drug: Liprotamase; Drug: porcine (pig) PERT	Phase 3

Detailed Description

Porcine derived enzymes are used for pancreatic enzyme replacement therapy in patients with cystic fibrosis (CF). Liprotamase is a biotechnology-derived enzyme replacement without enteric coating. This is an open-label, assessor blind, parallel group, multicenter, international trial to evaluate the noninferiority of liprotamase and pancrelipase in CF patients aged ≥7 years with pancreatic insufficiency. Subjects were randomized to liprotamase or pancrelipase, dose-matched to pre-study lipase doses. The lower bound of the 95% confidence interval (CI) for noninferiority was -15% for treatment difference in change from baseline coefficient of fat absorption (CFA).

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Open-Label, Assessor-Blind, Noninferiority, Active-Comparator Study Evaluating the Efficacy and Safety of Liprotamase in Subjects With Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency
• Actual Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Jan 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liprotamase Individually-optimized dose to be administered orally	Drug: Liprotamase; oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement
Active Comparator: porcine (pig) PERT Individually-optimized dose to be administered orally	Drug: porcine (pig) PERT; oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source

Outcome Measures

Primary Outcome Measures

1. Treatment Difference in Coefficient of Fat Absorption (CFA) Change From Baseline [Baseline, 7 weeks]

   The primary endpoint evaluates the difference between treatment arms in change from baseline in coefficient of fat absorption (CFA). As such, descriptive statistics for individual treatment arms are not provided in this measure, but are reported in the secondary endpoints

Secondary Outcome Measures

1. Coefficient of Fat Absorption (CFA) [Baseline, 7 weeks]

   Change from baseline in coefficient of fat absorption

2. Coefficient of Nitrogen Absorption (CNA) [Baseline, 7 weeks]

   Change from baseline in coefficient of nitrogen absorption

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of Cystic Fibrosis based on presentation, genotype and/or sweat chloride

• Fecal elastase <100 mcg/g stool

• Minimum Coefficient of Fat (CFA) at screening while on stable PERT therapy

• Good nutritional status

Exclusion Criteria:

• History or diagnosis of fibrosing colonopathy

• Distal intestinal obstruction syndrome in 6 months prior to screening

• Receiving enteral tube feedings

• Chronic diarrheal illness unrelated to pancreatic insufficiency

• Liver abnormalities, or liver or lung transplant, or significant bowel resection

• Forced expiratory volume in 1 second (FEV1) <30%

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site 123	Long Beach	California	United States	90806
2	Investigator Site 107	Los Angeles	California	United States	90033
3	Investigator Site 114	Aurora	Colorado	United States	80045
4	Investigator Site 120	Gainesville	Florida	United States	32610
5	Investigator Site 102	Jacksonville	Florida	United States	32207
6	Investigator Site 130	Miami	Florida	United States	33136
7	Investigator Site 117	Orlando	Florida	United States	32803
8	Investigator Site 110	Atlanta	Georgia	United States	30342
9	Investigator Site 127	Chicago	Illinois	United States	60611
10	Investigator Site 109	Glenview	Illinois	United States	60025
11	Investigator Site 104	Indianapolis	Indiana	United States	46202
12	Investigator Site 105	Wichita	Kansas	United States	67214
13	Investigator Site 128	Lexington	Kentucky	United States	40506
14	Investigator Site 122	Louisville	Kentucky	United States	40202
15	Investigator Site 132	Portland	Maine	United States	04102
16	Investigator Site 124	Ann Arbor	Michigan	United States	48109-5212
17	Investigator Site 126	East Lansing	Michigan	United States	48823
18	Investigator Site 134	Jackson	Mississippi	United States	39216
19	Investigator Site 135	Las Vegas	Nevada	United States	89107
20	Investigator Site 103	Cleveland	Ohio	United States	44106
21	Investigator Site 113	Toledo	Ohio	United States	43606
22	Investigator Site 101	Oklahoma City	Oklahoma	United States	73104
23	Investigator Site 136	Oklahoma City	Oklahoma	United States	73112
24	Investigator Site 119	Portland	Oregon	United States	97239
25	Investigator Site 106	Hershey	Pennsylvania	United States	17033
26	Investigator Site 115	Pittsburgh	Pennsylvania	United States	15224
27	Investigator Site 111	Dallas	Texas	United States	75390
28	Investigator Site 125	Fort Worth	Texas	United States	76104
29	Investigator Site 116	Houston	Texas	United States	77030
30	Investigator Site 121	Burlington	Vermont	United States	05405
31	Investigator Site 112	Richmond	Virginia	United States	23219
32	Investigator Site 129	Morgantown	West Virginia	United States	26506
33	Investigator Site 133	Edmonton	Alberta	Canada	T6G IC9
34	Investigator Site 501	Brno		Czechia	62500
35	Investigator Site 502	Plzen		Czechia	305 99
36	Investigator Site 305	Szeged	Csongrad County	Hungary	6720
37	Investigator Site 303	Debrecen	Hajdu-Bihar	Hungary	4031
38	Investigator Site 302	Torokbalint	Pest County	Hungary	2045
39	Investigator Site 304	Mosdos	Somogy County	Hungary	7257
40	Investigator Site 301	Ajka	Veszprem County	Hungary	8400
41	Investigator Site 601	Jerusalem		Israel	9124001
42	Investigator Site 208	Bialystok		Poland	15-044
43	Investigator Site 203	Karpacz		Poland	58-540
44	Investigator Site 206	Lodz		Poland	90-329
45	Investigator Site 201	Lublin		Poland	20-093
46	Investigator Site 205	Lublin		Poland	20-362
47	Investigator Site 202	Rabka Zdroj		Poland	34-700
48	Investigator Site 209	Rzeszow		Poland	35-312
49	Investigator Site 204	Sopot		Poland	81-713
50	Investigator Site 207	Warszawa		Poland	01-195
51	Investigator Site 403	Madrid		Spain	28006
52	Investigator Site 401	Madrid		Spain	28046
53	Investigator Site 402	Malaga		Spain	29009
54	Investigator Site 404	Valencia		Spain	46026

Sponsors and Collaborators

• Anthera Pharmaceuticals

Investigators

• Study Director: Monica Gangal, Anthera Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Anthera Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02279498
• Other Study ID Numbers: AN-EPI3331
• First Posted: Oct 31, 2014
• Last Update Posted: Aug 14, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Fibrosis

Study Results

Participant Flow

Arm/Group Title	Liprotamase	Porcine (Pig) PERT
Arm/Group Description	Individually-optimized dose to be administered orally Liprotamase: oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement	Individually-optimized dose to be administered orally porcine (pig) PERT: oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source
Period Title: Overall Study
STARTED	65	63
COMPLETED	47	59
NOT COMPLETED	18	4

Baseline Characteristics

Arm/Group Title	Liprotamase	Porcine (Pig) PERT	Total
Arm/Group Description	Individually-optimized dose to be administered orally Liprotamase: oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement	Individually-optimized dose to be administered orally porcine (pig) PERT: oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source	Total of all reporting groups
Overall Participants	65	63	128
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	22.5 (8.54)	21.0 (8.95)	21.8 (8.74)
Sex: Female, Male (Count of Participants)
Female	30 46.2%	31 49.2%	61 47.7%
Male	35 53.8%	32 50.8%	67 52.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 1.5%	0 0%	1 0.8%
Black or African American	0 0%	0 0%	0 0%
White	63 96.9%	61 96.8%	124 96.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.5%	2 3.2%	3 2.3%
Coefficient of fat absorption (CFA) (fat absorbed as percent of fat ingested) [Mean (Full Range) ]
Mean (Full Range) [fat absorbed as percent of fat ingested]	88.7	89.4	89.1
Coefficient of nitrogen absorption (CNA) (% of nitrogen ingested) [Mean (Full Range) ]
Mean (Full Range) [% of nitrogen ingested]	96.9	97.3	97.1
pre-randomization enzyme dose (lipase units/kg/day) [Mean (Full Range) ]
Mean (Full Range) [lipase units/kg/day]	6299	6264	6282

Outcome Measures

1. Primary Outcome

Title	Treatment Difference in Coefficient of Fat Absorption (CFA) Change From Baseline
Description	The primary endpoint evaluates the difference between treatment arms in change from baseline in coefficient of fat absorption (CFA). As such, descriptive statistics for individual treatment arms are not provided in this measure, but are reported in the secondary endpoints
Time Frame	Baseline, 7 weeks

Outcome Measure Data

Analysis Population Description

Analysis population evaluates all subjects who received at least one dose of study drug. Missing Visit 7 CFA values were multiply imputed using baseline CFA, baseline BMI, sex, age, acid suppression usage, and region.

Arm/Group Title	Treatment Difference
Arm/Group Description	analysed as LS mean difference in change in CFA from baseline for Liprotamase - Porcine enzymes
Measure Participants	128
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	-11.852

2. Secondary Outcome

Title	Coefficient of Fat Absorption (CFA)
Description	Change from baseline in coefficient of fat absorption
Time Frame	Baseline, 7 weeks

Outcome Measure Data

Analysis Population Description

Analysis population evaluates observed case data without multiple imputation for missing values

Arm/Group Title	Liprotamase	Porcine (Pig) PERT
Arm/Group Description	Individually-optimized dose to be administered orally Liprotamase: oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement	Individually-optimized dose to be administered orally porcine (pig) PERT: oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source
Measure Participants	53	62
Mean (Standard Deviation) [fat absorbed as % of fat ingested]	76.5 (16.13)	89.5 (5.84)

3. Secondary Outcome

Title	Coefficient of Nitrogen Absorption (CNA)
Description	Change from baseline in coefficient of nitrogen absorption
Time Frame	Baseline, 7 weeks

Outcome Measure Data

Analysis Population Description

Analysis population evaluates observed case data without multiple imputation for missing values

Arm/Group Title	Liprotamase	Porcine (Pig) PERT
Arm/Group Description	Individually-optimized dose to be administered orally Liprotamase: oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement	Individually-optimized dose to be administered orally porcine (pig) PERT: oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source
Measure Participants	53	62
Mean (Standard Deviation) [percent of nitrogen ingested]	95.8 (2.46)	97.5 (1.21)

Adverse Events

Time Frame	6 months
Arm/Group Title	Liprotamase		Porcine (Pig) PERT
Arm/Group Description	Individually-optimized dose to be administered orally Liprotamase: oral, soluble, non-enterically coated, non-porcine, pancreatic enzyme replacement		Individually-optimized dose to be administered orally porcine (pig) PERT: oral, enterically-coated, pancreatic replacement enzymes prepared from a porcine source
All Cause Mortality
	Liprotamase		Porcine (Pig) PERT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/63 (0%)
Serious Adverse Events
	Liprotamase		Porcine (Pig) PERT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/65 (10.8%)		6/63 (9.5%)
Gastrointestinal disorders
Constipation	1/65 (1.5%)	1	0/63 (0%)	0
Distal intestinal obstruction syndrome	1/65 (1.5%)	1	0/63 (0%)	0
General disorders
Systemic inflammatory response syndrome	1/65 (1.5%)	1	0/63 (0%)	0
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	3/65 (4.6%)	3	5/63 (7.9%)	5
Injury, poisoning and procedural complications
Tibia fracture	0/65 (0%)	0	1/63 (1.6%)	1
Investigations
Clostridium test positive	1/65 (1.5%)	1	0/63 (0%)	0
Renal and urinary disorders
Hydronephrosis	1/65 (1.5%)	1	0/63 (0%)	0
Other (Not Including Serious) Adverse Events
	Liprotamase		Porcine (Pig) PERT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/65 (63.1%)		38/63 (60.3%)
Gastrointestinal disorders
Constipation	2/65 (3.1%)	2	1/63 (1.6%)	1
Gastrooesophageal reflux disease	2/65 (3.1%)	2	1/63 (1.6%)	1
Nausea	2/65 (3.1%)	2	0/63 (0%)	0
General disorders
Pyrexia	1/65 (1.5%)	1	3/63 (4.8%)	3
Systemic inflammatory response syndrome	1/65 (1.5%)	1	0/63 (0%)	0
Chest discomfort	0/65 (0%)	0	1/63 (1.6%)	1
Infections and infestations
Infective pulmonary exacerbation	13/65 (20%)	13	17/63 (27%)	17
Nasopharyngitis	3/65 (4.6%)	3	1/63 (1.6%)	1
Bronchitis	2/65 (3.1%)	2	2/63 (3.2%)	2
Respiratory tract infection	4/65 (6.2%)	4	5/63 (7.9%)	5
Viral infection	2/65 (3.1%)	2	0/63 (0%)	0
Investigations
Alanine aminotransferase increased	2/65 (3.1%)	2	0/63 (0%)	0
Metabolism and nutrition disorders
Abnormal loss of weight	4/65 (6.2%)	4	1/63 (1.6%)	1
Nervous system disorders
Headache	4/65 (6.2%)	4	3/63 (4.8%)	3
Respiratory, thoracic and mediastinal disorders
Cough	2/65 (3.1%)	2	6/63 (9.5%)	6
Dyspnoea	2/65 (3.1%)	2	0/63 (0%)	0
Haemoptysis	2/65 (3.1%)	2	2/63 (3.2%)	2
Nasal congestion	2/65 (3.1%)	2	3/63 (4.8%)	3
Productive cough	2/65 (3.1%)	2	1/63 (1.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.