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Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Participants 1 to Less Than 2 Years of Age With Cystic Fibrosis, Homozygous for F508del

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03601637
Recruitment Status : Completed
First Posted : July 26, 2018
Results First Posted : January 6, 2023
Last Update Posted : January 6, 2023
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: LUM
Drug: IVA
Enrollment 61
Recruitment Details  
Pre-assignment Details This study was conducted in participants with cystic fibrosis (CF) aged 1 through less than 2 years of age who are homozygous for F508del. A total of 61 participants were enrolled in Parts A and B of the study. One participant in Part B was enrolled but not dosed in this study. Therefore, data for 60 participants are reported in the participant flow and baseline characteristics sections.
Arm/Group Title Part A: LUM/IVA Part B: LUM/IVA
Hide Arm/Group Description Participants weighing 7 to less than( <)10 kilograms (kg) at screening received lumacaftor (LUM) 75 milligrams (mg)/ ivacaftor (IVA) 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants weighing greater than or equal to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. Participants weighing 7 to <9 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight.
Period Title: Overall Study
Started 14 46
Completed 13 43
Not Completed 1 3
Reason Not Completed
Withdrawal of Consent (not due to adverse event)             0             1
Adverse Event             1             1
Other             0             1
Arm/Group Title Part A: LUM/IVA Part B: LUM/IVA Total
Hide Arm/Group Description Participants weighing 7 to less than(<)10 kilograms (kg) at screening received lumacaftor (LUM) 75 milligrams (mg)/ ivacaftor (IVA) 94 mg fixed-dose combination (FDC) every 12 hours (q12h) and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants weighing greater than or equal to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. Participants weighing 7 to <9 kg at screening received LUM 75 mg/ IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight. Total of all reporting groups
Overall Number of Baseline Participants 14 46 60
Hide Baseline Analysis Population Description
All participants who received at least one dose of the study drug during the treatment period were included in the baseline analysis. The baseline analysis was collected for the overall treatment arm, irrespective of a weight-based dose regimen. Therefore, the analysis is reported in a single arm for each study part (Part A: LUM/IVA and Part B: LUM/IVA).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 46 participants 60 participants
<=18 years
14
 100.0%
46
 100.0%
60
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 46 participants 60 participants
Female
7
  50.0%
24
  52.2%
31
  51.7%
Male
7
  50.0%
22
  47.8%
29
  48.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 46 participants 60 participants
Hispanic or Latino
1
   7.1%
2
   4.3%
3
   5.0%
Not Hispanic or Latino
13
  92.9%
37
  80.4%
50
  83.3%
Unknown or Not Reported
0
   0.0%
7
  15.2%
7
  11.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 46 participants 60 participants
White
14
 100.0%
34
  73.9%
48
  80.0%
Black or African American
0
   0.0%
1
   2.2%
1
   1.7%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
American Indian or Alaska Native
0
   0.0%
1
   2.2%
1
   1.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Not collected per local regulations
0
   0.0%
7
  15.2%
7
  11.7%
Other
0
   0.0%
3
   6.5%
3
   5.0%
1.Primary Outcome
Title Part A: Observed Plasma Concentrations From 3-4 Hours (C3-4hr) of LUM and IVA
Hide Description [Not Specified]
Time Frame Day 1 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point.
Arm/Group Title Part A: LUM 75 mg/IVA 94 mg Part A: LUM 100 mg/IVA 125 mg
Hide Arm/Group Description:
Participants received LUM 75 mg /IVA 94 mg dose every 12 hours for 15 days.
Participants received LUM 100 mg/IVA 125 mg dose 2 every 12 hours for 15 days.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
Day 1: LUM Number Analyzed 7 participants 7 participants
14600  (5560) 12600  (7190)
Day 15: LUM Number Analyzed 7 participants 5 participants
16600  (9590) 13900  (5800)
Day 1: IVA Number Analyzed 7 participants 7 participants
1620  (648) 1320  (804)
Day 15: IVA Number Analyzed 7 participants 5 participants
718  (352) 496  (268)
2.Primary Outcome
Title Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA
Hide Description [Not Specified]
Time Frame Pre-dose at Day 8 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point.
Arm/Group Title Part A: LUM 75 mg/IVA 94 mg Part A: LUM 100 mg/IVA 125 mg
Hide Arm/Group Description:
Participants received LUM 75 mg/IVA 94 mg dose every 12 hours for 15 days.
Participants received LUM 100 mg/IVA125 mg dose every 12 hours for 15 days.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 8: LUM Number Analyzed 7 participants 6 participants
12000  (8880) 12800  (3900)
Day 15: LUM Number Analyzed 5 participants 6 participants
8380  (7790) 10500  (3070)
Day 8: IVA Number Analyzed 7 participants 6 participants
169  (75.5) 185  (101)
Day 15: IVA Number Analyzed 5 participants 6 participants
78.9  (19.1) 120  (60.5)
3.Primary Outcome
Title Part B : Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame From Day 1 up to Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included all participants who received at least 1 dose of study drug in the treatment period. The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part B: LUM/IVA arm.
Arm/Group Title Part B: LUM/IVA
Hide Arm/Group Description:
Participants weighing 7 to <9 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg FDC q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight.
Overall Number of Participants Analyzed 46
Measure Type: Number
Unit of Measure: participants
Participants with TEAEs 44
Participants with SAEs 5
4.Secondary Outcome
Title Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame From Day 1 up to Day 25
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set included all participants who received at least 1 dose of study drug in the treatment period. The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part A: LUM/IVA arm.
Arm/Group Title Part A: LUM/IVA
Hide Arm/Group Description:
Participants weighing 7 to <10 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg FDC q12h for 15 days. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days.
Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: participants
Participants with TEAEs 12
Participants with SAEs 0
5.Secondary Outcome
Title Part A: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA)
Hide Description [Not Specified]
Time Frame Pre-dose at Day 8 and Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed signifies those participants who were evaluable at specified time point.
Arm/Group Title Part A: LUM 75 mg/IVA 94 mg Part A: LUM 100 mg/IVA 125 mg
Hide Arm/Group Description:
Participants received LUM 75 mg/IVA 94 mg dose every 12 hours for 15 days.
Participants received LUM 100 mg/IVA125 mg dose every 12 hours for 15 days.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 8: M28-LUM Number Analyzed 7 participants 6 participants
1410  (791) 1470  (365)
Day 15: M28-LUM Number Analyzed 5 participants 6 participants
1460  (1060) 1370  (468)
Day 8: M1-IVA Number Analyzed 7 participants 6 participants
606  (298) 842  (527)
Day 15: M1-IVA Number Analyzed 5 participants 6 participants
284  (70.2) 604  (394)
Day 8: M6-IVA Number Analyzed 7 participants 6 participants
2380  (843) 3290  (1830)
Day 15: M6-IVA Number Analyzed 5 participants 6 participants
1460  (763) 2800  (2300)
6.Secondary Outcome
Title Part B: Absolute Change in Sweat Chloride
Hide Description [Not Specified]
Time Frame From Baseline at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set (FAS) included all enrolled participants who were exposed to any amount of study drug in Part B.The pharmacodynamic analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single Part B: LUM/IVA arm.
Arm/Group Title Part B: LUM/IVA
Hide Arm/Group Description:
Participants weighing 7 to <9 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg FDC q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight.
Overall Number of Participants Analyzed 46
Mean (Standard Deviation)
Unit of Measure: Millimole per liter (mmol/L)
-29.1  (13.5)
7.Secondary Outcome
Title Part B: Observed Pre-dose Plasma Concentration (Ctrough) of LUM and IVA and Their Respective Metabolites (M28-LUM, M1-IVA and M6-IVA)
Hide Description [Not Specified]
Time Frame Pre-dose at Day 15, Week 4, Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
PK set included participants who received at least 1 dose of study drug. Here the "Number Analyzed" signifies those participants who were evaluable at specified time point.
Arm/Group Title Part B: LUM 75 mg/IVA 94 mg Part B: LUM 100 mg/IVA 125 mg Part B: LUM 150 mg/IVA 188 mg
Hide Arm/Group Description:
Participants received LUM 75 mg/IVA 94 mg dose every 12 hours for 24 weeks.
Participants received LUM 100 mg/IVA 125 mg dose every 12 hours for 24 weeks.
Participants received LUM 150 mg/IVA 188 mg dose every 12 hours for 24 weeks.
Overall Number of Participants Analyzed 1 44 1
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 15: LUM Number Analyzed 1 participants 43 participants 1 participants
13500 9030  (4390) 887
Week 4: LUM Number Analyzed 1 participants 43 participants 1 participants
21900 9370  (5030) 1000
Week 12: LUM Number Analyzed 1 participants 41 participants 1 participants
12100 9160  (4400) 566
Week 24: LUM Number Analyzed 1 participants 35 participants 1 participants
11200 8930  (5310) 288
Day 15: M28-LUM Number Analyzed 1 participants 43 participants 1 participants
1460 1260  (528) 786
Week 4: M28-LUM Number Analyzed 1 participants 43 participants 1 participants
1570 1340  (579) 602
Week 12: M28-LUM Number Analyzed 1 participants 41 participants 1 participants
1740 1440  (599) 501
Week 24: M28-LUM Number Analyzed 1 participants 35 participants 1 participants
1870 1470  (548) 569
Day 15: IVA Number Analyzed 1 participants 43 participants 1 participants
213 112  (68.3) 3.68
Week 4: IVA Number Analyzed 1 participants 43 participants 1 participants
267 112  (82.9) 11.4
Week 12: IVA Number Analyzed 1 participants 41 participants 1 participants
286 91.7  (44.7) 2.18
Week 24: IVA Number Analyzed 1 participants 34 participants 1 participants
37.1 144  (296) 2.86
Day 15: M1-IVA Number Analyzed 1 participants 43 participants 1 participants
1420 437  (291) 18.1
Week 4: M1-IVA Number Analyzed 1 participants 43 participants 1 participants
1930 466  (359) 58.0
Week 12: M1-IVA Number Analyzed 1 participants 41 participants 1 participants
759 418  (236) 18.3
Week 24: M1-IVA Number Analyzed 1 participants 35 participants 1 participants
256 499  (613) 18.5
Day 15: M6-IVA Number Analyzed 1 participants 43 participants 1 participants
4740 1930  (1460) 43.9
Week 4: M6-IVA Number Analyzed 1 participants 43 participants 1 participants
9090 1970  (1490) 131
Week 12: M6-IVA Number Analyzed 1 participants 41 participants 1 participants
3520 1950  (1430) 46.5
Week 24: M6-IVA Number Analyzed 1 participants 35 participants 1 participants
1320 1740  (1130) 63.3
Time Frame From Day 1 Through Safety Follow-up Period (up to Day 25 for Part A and up to Week 26 for Part B)
Adverse Event Reporting Description The safety and tolerability analyses were assessed for the overall treatment arm, irrespective of weight-based dose regimen. Therefore, the analysis is reported in a single arm for each study part (Part A: LUM/IVA and Part B: LUM/IVA).
 
Arm/Group Title Part A: LUM/IVA Part B: LUM/IVA
Hide Arm/Group Description Participants weighing 7 to <10 kg at screening received LUM 75 mg/IVA 94 mg FDC q12h and those weighing 10 to <14 kg at screening received LUM 100 mg/IVA 125 mg q12h for 15 days. Participants >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 15 days. Participants weighing 7 to <9 kg at screening received LUM 75 mg/ IVA 94 mg FDC q12h and those weighing 9 to <14 kg received LUM 100 mg/IVA 125 mg FDC q12h for 24 weeks. Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h for 24 weeks. Doses were adjusted upwards for changes in weight.
All-Cause Mortality
Part A: LUM/IVA Part B: LUM/IVA
Affected / at Risk (%) Affected / at Risk (%)
Total   0/14 (0.00%)   0/46 (0.00%) 
Hide Serious Adverse Events
Part A: LUM/IVA Part B: LUM/IVA
Affected / at Risk (%) Affected / at Risk (%)
Total   0/14 (0.00%)   5/46 (10.87%) 
Gastrointestinal disorders     
Distal intestinal obstruction syndrome  1  0/14 (0.00%)  1/46 (2.17%) 
Infections and infestations     
Infective pulmonary exacerbation of cystic fibrosis  1  0/14 (0.00%)  3/46 (6.52%) 
Injury, poisoning and procedural complications     
Post procedural fever  1  0/14 (0.00%)  1/46 (2.17%) 
1
Term from vocabulary, MedDRA (24.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: LUM/IVA Part B: LUM/IVA
Affected / at Risk (%) Affected / at Risk (%)
Total   12/14 (85.71%)   42/46 (91.30%) 
Gastrointestinal disorders     
Abdominal pain  1  0/14 (0.00%)  3/46 (6.52%) 
Constipation  1  1/14 (7.14%)  5/46 (10.87%) 
Diarrhoea  1  0/14 (0.00%)  3/46 (6.52%) 
Flatulence  1  1/14 (7.14%)  1/46 (2.17%) 
Vomiting  1  0/14 (0.00%)  8/46 (17.39%) 
General disorders     
Crying  1  1/14 (7.14%)  0/46 (0.00%) 
Pyrexia  1  1/14 (7.14%)  10/46 (21.74%) 
Infections and infestations     
Ear infection  1  0/14 (0.00%)  5/46 (10.87%) 
Infective pulmonary exacerbation of cystic fibrosis  1  0/14 (0.00%)  8/46 (17.39%) 
Influenza  1  2/14 (14.29%)  0/46 (0.00%) 
Nasopharyngitis  1  0/14 (0.00%)  4/46 (8.70%) 
Viral upper respiratory tract infection  1  0/14 (0.00%)  5/46 (10.87%) 
Upper respiratory tract infection  1  1/14 (7.14%)  6/46 (13.04%) 
Injury, poisoning and procedural complications     
Lip injury  1  1/14 (7.14%)  0/46 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  0/14 (0.00%)  4/46 (8.70%) 
Pseudomonas test positive  1  0/14 (0.00%)  5/46 (10.87%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/14 (7.14%)  1/46 (2.17%) 
Psychiatric disorders     
Insomnia  1  1/14 (7.14%)  1/46 (2.17%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/14 (28.57%)  16/46 (34.78%) 
Nasal congestion  1  1/14 (7.14%)  4/46 (8.70%) 
Rhinorrhoea  1  5/14 (35.71%)  5/46 (10.87%) 
Skin and subcutaneous tissue disorders     
Rash  1  3/14 (21.43%)  4/46 (8.70%) 
1
Term from vocabulary, MedDRA (24.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Monitor
Organization: Vertex Pharmaceuticals Incorporated
Phone: 617-341-6777
EMail: medicalinfo@vrtx.com
Layout table for additonal information
Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03601637    
Other Study ID Numbers: VX16-809-122
2017-004794-13 ( EudraCT Number )
First Submitted: July 18, 2018
First Posted: July 26, 2018
Results First Submitted: October 28, 2022
Results First Posted: January 6, 2023
Last Update Posted: January 6, 2023