Trial Outcomes & Findings for Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis (NCT NCT01859390)

Last Updated: 2017-07-14

Results Overview

The primary outcome is the difference in 16 week mean change in log10 sputum myeloperoxidase levels between the AquADEKs-2 arm and the Control Multivitamin arm.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

73 participants

Primary outcome timeframe

Baseline (Visit 2) to Week 16 (Visit 4)

Results posted on

2017-07-14

Participant Flow

Participant milestones

Participant milestones
Measure	AquADEKs-2 Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Overall Study STARTED	36	37
Overall Study Withdrawals	2	2
Overall Study COMPLETED	35	30
Overall Study NOT COMPLETED	1	7

Reasons for withdrawal

Reasons for withdrawal
Measure	AquADEKs-2 Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Overall Study Insufficient Sputum Collected	1	3
Overall Study Sample Missing Collection Date	0	1
Overall Study Tube Cracked	0	2
Overall Study Shipment Error	0	1

Baseline Characteristics

Effects of an Antioxidant-Enriched Multivitamin Supplement on Inflammation and Oxidative Stress in Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AquADEKs-2 n=36 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Total n=73 Participants Total of all reporting groups
Age, Continuous	22.3 years STANDARD_DEVIATION 8.9 • n=5 Participants	22.9 years STANDARD_DEVIATION 9.5 • n=7 Participants	22.6 years STANDARD_DEVIATION 9.1 • n=5 Participants
Age, Customized Age >=10 - <18 yrs	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Age, Customized Age >=18 - <30 yrs	17 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants
Age, Customized Age >30 yrs	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Caucasian	34 Participants n=5 Participants	30 Participants n=7 Participants	64 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Hispanic	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · African-American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race/Ethnicity · Unknown/Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Cystic Fibrosis (CF) Genotype Delta F508 Homozygous	23 Participants n=5 Participants	16 Participants n=7 Participants	39 Participants n=5 Participants
Cystic Fibrosis (CF) Genotype Delta F508 Heterozygous	9 Participants n=5 Participants	18 Participants n=7 Participants	27 Participants n=5 Participants
Cystic Fibrosis (CF) Genotype Other	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Cystic Fibrosis (CF) Genotype Not Identified	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Visit 2) to Week 16 (Visit 4)

The primary outcome is the difference in 16 week mean change in log10 sputum myeloperoxidase levels between the AquADEKs-2 arm and the Control Multivitamin arm.

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=35 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=30 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Change in Sputum Myeloperoxidase (MPO) Level	-0.10 log10 (ng/mL) Standard Deviation 0.67	0.03 log10 (ng/mL) Standard Deviation 0.76

SECONDARY outcome

Timeframe: 18 weeks follow up

Incidence is defined as the number and percentage of participants with at least one event over the 18 week follow-up period.

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=36 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Incidence of AEs	33 Participants	34 Participants
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Incidence of SAEs	8 Participants	13 Participants

SECONDARY outcome

Timeframe: 18 weeks follow up

Rate is defined as the number of events per participant follow-up week.

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=36 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) Number of AEs per participant week	0.34 events per participant-week	0.37 events per participant-week
Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) Number of SAEs per participant week	0.04 events per participant-week	0.05 events per participant-week

SECONDARY outcome

Timeframe: Baseline (Visit 2) to Week 16

Population: This population includes participants who did not complete the study (i.e., did not have a final analyzable sputum sample) but did have a final lung function assessment.

Absolute Change in Forced Expiratory Volume over one second (FEV1) % predicted between Baseline and Week 16. Global Lung Initiative equations were used to calculate FEV1 %predicted.

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=34 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=35 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Change in Lung Function	-0.76 FEV1 %Predicted Standard Deviation 8.00	-2.20 FEV1 %Predicted Standard Deviation 7.53

SECONDARY outcome

Timeframe: Baseline (Visit 2) to Week 16

Population: This population includes participants who did not complete the study (i.e., did not have a final analyzable sputum sample) but did have final height and weight assessments.

Absolute change in Body Mass Index (BMI) (kg/m\^2) between Baseline and Week 16.

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=34 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=34 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Change in Growth Endpoints	0.16 kg/m^2 Standard Deviation 0.68	0.13 kg/m^2 Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline (Visit 2) to end of follow up (Week 18)

Median time to first pulmonary exacerbation (PEx) between baseline (Visit 2) and end of follow up (Week 18)

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=36 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Time to First Pulmonary Exacerbation	102 days Interval 78.0 to The upper bound of the confidence interval could not be computed due to the distribution of events in the AquADEKs-2 arm.	96 days Interval 35.0 to 125.0

SECONDARY outcome

Timeframe: Baseline (Visit 2) to end of follow up (Week 18)

The total number of PEx between baseline (Visit 2) and end of follow up (Week 18).

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=36 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Number of Pulmonary Exacerbations	28 Pulmonary Exacerbations	39 Pulmonary Exacerbations

SECONDARY outcome

Timeframe: Baseline (Visit 2) to end of follow up (Week 18)

Number (%) with at least one protocol-defined PEx between baseline (Visit 2) and end of follow up (Week 18).

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=36 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Number of Participants With Pulmonary Exacerbations	19 Participants	25 Participants

SECONDARY outcome

Timeframe: Baseline (Visit 2) to end of followup (Week 18)

Number (%) of participants with at least one hospitalization between Baseline (Visit 2) and end of follow up (Week 18).

Outcome measures

Outcome measures
Measure	AquADEKs-2 n=36 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 Participants Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Number of Participants Hospitalized	7 Participants	13 Participants

Adverse Events

AquADEKs-2

Serious events: 8 serious events

Other events: 33 other events

Deaths: 0 deaths

Control Multivitamin

Serious events: 13 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Scott Sagel, Professor of Pediatrics

University of Colorado School of Medicine

Phone: 720-777-2522

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	AquADEKs-2 n=36 participants at risk Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 participants at risk Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Cardiac disorders Palpitations	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Eye disorders Eye swelling	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Asthenia	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Chest discomfort	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Chest pain	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Fatigue	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Pyrexia	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Breath sounds abnormal	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Chest X-ray abnormal	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Forced expiratory volume decreased	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Pulmonary function test decreased	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	8.1% 3/37 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Weight decreased	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Renal and urinary disorders Nephrolithiasis	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Bronchial wall thickening	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 3/36 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	16.2% 6/37 • Number of events 6 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Sputum increased	8.3% 3/36 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	8.1% 3/37 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Throat tightness	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Skin and subcutaneous tissue disorders Swelling face	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Vascular disorders Flushing	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.

Measure	AquADEKs-2 n=36 participants at risk Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period. For those subjects randomized to the AquADEKs-2 arm, two AquADEKs-2 softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 16 weeks. AquADEKs-2: AquADEKs-2 contains standard amounts of fat-soluble vitamins (A, D, E, K) that are contained in typical CF multivitamin supplements plus several antioxidants including beta-carotene, mixed tocopherols (different forms of vitamin E), coenzyme Q10 (CoQ10), mixed carotenoids (lutein, lycopene and zeaxanthin), and the minerals zinc and selenium. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.	Control Multivitamin n=37 participants at risk Two control multivitamin softgel capsules will be taken orally on a once daily basis with pancreatic enzymes and a glass of milk or fat-containing meal for 4 weeks for the screening run in period for all participants and for 16 weeks for those randomized to this comparative therapy. control multivitamin: The control multivitamin contains standard (standard for CF multivitamin supplements) amounts of vitamins A, B, D, E, and K without added antioxidants.
Gastrointestinal disorders Abdominal pain	11.1% 4/36 • Number of events 5 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	21.6% 8/37 • Number of events 11 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Gastrointestinal disorders Constipation	2.8% 1/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	10.8% 4/37 • Number of events 4 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Gastrointestinal disorders Diarrhoea	11.1% 4/36 • Number of events 4 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Gastrointestinal disorders Flatulence	8.3% 3/36 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 5 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Gastrointestinal disorders Nausea	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Gastrointestinal disorders Toothache	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Gastrointestinal disorders Vomiting	11.1% 4/36 • Number of events 5 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Asthenia	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Chest pain	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Fatigue	11.1% 4/36 • Number of events 4 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	13.5% 5/37 • Number of events 7 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
General disorders Pyrexia	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	13.5% 5/37 • Number of events 6 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Infections and infestations Pharyngitis	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Forced expiratory volume decreased	5.6% 2/36 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Pseudomonas test positive	0.00% 0/36 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	5.4% 2/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Pulmonary function test decreased	16.7% 6/36 • Number of events 9 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	24.3% 9/37 • Number of events 10 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Investigations Weight decreased	8.3% 3/36 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	8.1% 3/37 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Nervous system disorders Headache	11.1% 4/36 • Number of events 7 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	13.5% 5/37 • Number of events 5 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Nervous system disorders Sinus headache	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Psychiatric disorders Anxiety	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	0.00% 0/37 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Psychiatric disorders Decreased activity	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Psychiatric disorders Depression	2.8% 1/36 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	8.1% 3/37 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Cough	61.1% 22/36 • Number of events 30 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	51.4% 19/37 • Number of events 30 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 4/36 • Number of events 5 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	21.6% 8/37 • Number of events 8 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	11.1% 4/36 • Number of events 4 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	13.5% 5/37 • Number of events 6 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	19.4% 7/36 • Number of events 11 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	21.6% 8/37 • Number of events 8 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.1% 4/36 • Number of events 6 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Rales	8.3% 3/36 • Number of events 4 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	18.9% 7/37 • Number of events 8 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	11.1% 4/36 • Number of events 4 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	21.6% 8/37 • Number of events 8 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	11.1% 4/36 • Number of events 5 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	10.8% 4/37 • Number of events 5 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	11.1% 4/36 • Number of events 4 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	8.1% 3/37 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Sputum discoloured	8.3% 3/36 • Number of events 3 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Sputum increased	30.6% 11/36 • Number of events 14 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	27.0% 10/37 • Number of events 12 • Participant adverse event data was collected for the 4 months that subjects were on study drug.
Respiratory, thoracic and mediastinal disorders Wheezing	5.6% 2/36 • Number of events 2 • Participant adverse event data was collected for the 4 months that subjects were on study drug.	2.7% 1/37 • Number of events 1 • Participant adverse event data was collected for the 4 months that subjects were on study drug.