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Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation

Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Completed
CT.gov ID
NCT01225211
Collaborator
(none)
312
Enrollment
56
Locations
10
Arms
42
Duration (Months)
5.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
312 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Apr 1, 2014
Actual Study Completion Date :
Apr 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Cohort 1: Placebo

Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21).

Drug: Lumacaftor Placebo
Matching placebo tablet.

Drug: Ivacaftor Placebo
Matching placebo tablet.
Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h

Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21).

Drug: Lumacaftor
Tablet
Other Names:
  • VX-809, LUM

    • Drug: Ivacaftor
    Tablet.
    Other Names:
  • VX-770, IVA

    		•
    Experimental: Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h

    Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).

    Drug: Lumacaftor
    Tablet
    Other Names:
  • VX-809, LUM

    • Drug: Ivacaftor
    Tablet.
    Other Names:
  • VX-770, IVA

    		•
    Placebo Comparator: Cohort 2 and 3: Placebo (HO and HE)

    Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).

    Drug: Lumacaftor Placebo
    Matching placebo tablet.

    Drug: Ivacaftor Placebo
    Matching placebo tablet.
    Experimental: Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO)

    Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

    Drug: Lumacaftor
    Tablet
    Other Names:
  • VX-809, LUM

    • Drug: Ivacaftor
    Tablet.
    Other Names:
  • VX-770, IVA

    		•
    Experimental: Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO)

    Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

    Drug: Lumacaftor
    Tablet
    Other Names:
  • VX-809, LUM

    • Drug: Ivacaftor
    Tablet.
    Other Names:
  • VX-770, IVA

    		•
    Experimental: Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE)

    Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

    Drug: Lumacaftor
    Tablet
    Other Names:
  • VX-809, LUM

    • Drug: Ivacaftor
    Tablet.
    Other Names:
  • VX-770, IVA

    		•
    Experimental: Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO)

    Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).

    Drug: Lumacaftor
    Tablet
    Other Names:
  • VX-809, LUM

    • Drug: Ivacaftor
    Tablet.
    Other Names:
  • VX-770, IVA

    		•
    Placebo Comparator: Cohort 4: Placebo

    Participants heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 1 through Day 56).

    Drug: Lumacaftor Placebo
    Matching placebo tablet.

    Drug: Ivacaftor Placebo
    Matching placebo tablet.
    Experimental: Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h

    Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).

    Drug: Lumacaftor
    Tablet
    Other Names:
  • VX-809, LUM

    • Drug: Ivacaftor
    Tablet.
    Other Names:
  • VX-770, IVA

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Cohort 1: Safety and Tolerability Based on Adverse Events (AEs) [Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)]

      AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).

    2. Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs) [Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)]

      Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).

    3. Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs [Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)]

      AEs and SAEs are defined in Outcome Measure 1.

    4. Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21 [Cohort 1: Day 14, Day 21]

    5. Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56 [Cohort 2 and 3: Day 28, Day 56]

    6. Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56 [Cohort 4: Baseline, Day 56]

      FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.

    Secondary Outcome Measures

    1. Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14 [Cohort 1: Baseline, Day 14]

    2. Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14 [Cohort 2: Baseline, Day 14]

    3. Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56 [Cohort 4: Baseline, Day 56]

    4. Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21 [Cohort 1: Day 14, Day 21]

      FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    5. Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21 [Cohort 1: Day 14, Day 21]

      FEV1 and ppFEV1 are defined in Outcome Measure 6.

    6. Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56 [Cohort 2 and 3: Day 28, Day 56]

      FEV1 and ppFEV1 are defined in Outcome Measure 6.

    7. Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56 [Cohort 2 and 3: Day 28, Day 56]

      FEV1 and ppFEV1 are defined in Outcome Measure 6.

    8. Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56 [Cohort 2 and 3: Baseline, Day 28 and 56]

      FEV1 and ppFEV1 are defined in Outcome Measure 6.

    9. Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56 [Cohort 2 and 3: Baseline, Day 28 and 56]

      FEV1 and ppFEV1 are defined in Outcome Measure 6.

    10. Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56 [Cohort 4: Baseline, Day 56]

      FEV1 and ppFEV1 are defined in Outcome Measure 6.

    11. Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56 [Cohort 2 and 3: Day 28, Day 56]

      The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.

    12. Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56 [Cohort 4: Baseline, Day 56]

      CFQ-R respiratory domain is defined in Outcome Measure 17.

    13. Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56 [Cohort 4: Baseline, Day 56]

      BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).

    14. Cohort 4: Absolute Change From Baseline in Weight at Day 56 [Cohort 4: Baseline, Day 56]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female participants with confirmed diagnosis of CF

    • Must have the F508del-CFTR mutation on at least 1 allele.

    • FEV1 greater than equal (>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)

    • Participant of child-bearing potential and who are sexually active must meet the contraception requirements

    Exclusion Criteria:

    • History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the participant (e.g., cirrhosis with portal hypertension).

    • An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.

    • History of solid organ or hematological transplantation.

    • History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.

    • Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout

    • Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception

    • Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3

    • Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit

    • Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4

    • Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States
    2 Anchorage Alaska United States
    3 La Jolla California United States
    4 Long Beach California United States
    5 Palo Alto California United States
    6 Sacramento California United States
    7 Denver Colorado United States
    8 New Haven Connecticut United States
    9 Miami Florida United States
    10 Orlando Florida United States
    11 Tampa Florida United States
    12 Atlanta Georgia United States
    13 Boise Idaho United States
    14 Chicago Illinois United States
    15 Iowa City Iowa United States
    16 Kansas City Kansas United States
    17 Lexington Kentucky United States
    18 New Orleans Louisiana United States
    19 Baltimore Maryland United States
    20 Boston Massachusetts United States
    21 Minneapolis Minnesota United States
    22 St. Louis Missouri United States
    23 Omaha Nebraska United States
    24 Lebanon New Hampshire United States
    25 Buffalo New York United States
    26 New Hyde Park New York United States
    27 New York New York United States
    28 Rochester New York United States
    29 Syracuse New York United States
    30 Chapel Hill North Carolina United States
    31 Akron Ohio United States
    32 Cleveland Ohio United States
    33 Columbus Ohio United States
    34 Oklahoma City Oklahoma United States
    35 Philadelphia Pennsylvania United States
    36 Pittsburgh Pennsylvania United States
    37 Pittsburg Pennsylvania United States
    38 Charleston South Carolina United States
    39 Sioux Falls South Dakota United States
    40 Adelaide Australia
    41 Brisbane Australia
    42 Chermside Australia
    43 Nedlands Australia
    44 Parkville Victoria Australia
    45 Westmead Australia
    46 Leuven Belgium
    47 Pierre Benite Cedex Rhone France
    48 Paris France
    49 Jena Thueringen Germany
    50 Berlin Germany
    51 Bochum Germany
    52 Essen Germany
    53 Koeln Germany
    54 Auckland New Zealand
    55 Christchurch New Zealand
    56 London United Kingdom

    Sponsors and Collaborators

    • Vertex Pharmaceuticals Incorporated

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT01225211
    Other Study ID Numbers:
    • VX09-809-102
    • 2010-020413-90
    First Posted:
    Oct 20, 2010
    Last Update Posted:
    Oct 5, 2015
    Last Verified:
    Sep 1, 2015
    Additional relevant MeSH terms:
    Cystic Fibrosis
    Fibrosis
    Ivacaftor

    Study Results

    Participant Flow

    Recruitment Details Participants in each cohort are mutually exclusive. A total of 312 participants were randomized of which one participant did not receive any treatment and a total of 311 participants were treated.
    Pre-assignment Detail Study included 4 cohorts which were studied in sequential manner. For results reporting, combined placebo arm was reported for Cohort 2 and 3 and results for these 2 cohorts are reported collectively.
    Arm/Group Title Cohort 1: Placebo Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h Cohort 2 and 3: Placebo (HO and HE) Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE) Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants homozygous (HO) for the F508del-CF transmembrane conductance regulator gene (CFTR) mutation received lumacaftor matched placebo once daily (qd) (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo every 12 hours (q12h) (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 milligram (mg) of lumacaftor (LUM) qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor (IVA) q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Period Title: Overall Study
    STARTED 21 20 21 27 23 21 42 11 63 62
    COMPLETED 21 20 20 27 23 21 41 11 62 57
    NOT COMPLETED 0 0 1 0 0 0 1 0 1 5

    Baseline Characteristics

    Arm/Group Title Cohort 1: Placebo Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 150 mg q12h Cohort 1: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h Cohort 2 and 3: Placebo (HO and HE) Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO&HE) Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h Total
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 14), followed by lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56). Total of all reporting groups
    Overall Participants 21 20 21 27 23 21 42 11 63 62 311
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    21
    100%
    20
    100%
    21
    100%
    27
    100%
    23
    100%
    21
    100%
    42
    100%
    11
    100%
    63
    100%
    62
    100%
    311
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    10
    47.6%
    8
    40%
    13
    61.9%
    9
    33.3%
    11
    47.8%
    9
    42.9%
    19
    45.2%
    5
    45.5%
    31
    49.2%
    29
    46.8%
    144
    46.3%
    Male
    11
    52.4%
    12
    60%
    8
    38.1%
    18
    66.7%
    12
    52.2%
    12
    57.1%
    23
    54.8%
    6
    54.5%
    32
    50.8%
    33
    53.2%
    167
    53.7%

    Outcome Measures

    1. Primary Outcome
    Title Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)
    Description AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).
    Time Frame Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)

    Outcome Measure Data

    Analysis Population Description
    Cohort 1 Safety Set included all participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 1: Placebo - Period 1 Cohort 1: LUM 200 mg qd - Period 1 Cohort 1: Placebo - Period 2 Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 14). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14). Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21).
    Measure Participants 21 41 21 20 20
    Participants with any AEs
    12
    57.1%
    29
    145%
    15
    71.4%
    14
    51.9%
    12
    52.2%
    Participants with SAEs
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)
    Description Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).
    Time Frame Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Safety Set included all participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2 and 3: Placebo (HO and HE) - Period 1 Cohort 2: LUM 200 mg qd - Period 1 Cohort 2: LUM 400 mg qd - Period 1 Cohort 2: LUM 600 mg qd - Period 1 Cohort 3: LUM 400 mg q12h - Period 1 Cohort 2 and 3: Placebo (HO and HE) - Period 2 Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO&HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2
    Arm/Group Description Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56).
    Measure Participants 27 23 21 42 11 27 21 20 38 11
    Participants with any AEs
    23
    109.5%
    18
    90%
    18
    85.7%
    37
    137%
    7
    30.4%
    20
    95.2%
    12
    28.6%
    15
    136.4%
    26
    41.3%
    10
    16.1%
    Participants with SAEs
    1
    4.8%
    2
    10%
    0
    0%
    3
    11.1%
    2
    8.7%
    4
    19%
    0
    0%
    1
    9.1%
    4
    6.3%
    1
    1.6%
    3. Primary Outcome
    Title Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs
    Description AEs and SAEs are defined in Outcome Measure 1.
    Time Frame Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)

    Outcome Measure Data

    Analysis Population Description
    Cohort 4 Safety Set included all participants who received at least 1 dose of study drug in Cohort 4.
    Arm/Group Title Cohort 4: Placebo Cohort 4: Active Study Drug
    Arm/Group Description Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Measure Participants 63 62
    Participants with any AEs
    53
    252.4%
    52
    260%
    Participants with SAEs
    5
    23.8%
    9
    45%
    4. Primary Outcome
    Title Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21
    Description
    Time Frame Cohort 1: Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 Cohort 1: Placebo - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21).
    Measure Participants 19 14 17
    Least Squares Mean (95% Confidence Interval) [millimole per liter (mmol/L)]
    -2.131
    -9.128
    0.548
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo - Period 1, Cohort 1: Placebo - Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.267
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -2.679
    Confidence Interval (2-Sided) 95%
    -7.484 to 2.125
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: LUM 200 mg qd - Period 1, Cohort 1: Placebo - Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -9.676
    Confidence Interval (2-Sided) 95%
    -14.801 to -4.551
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Primary Outcome
    Title Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56
    Description
    Time Frame Cohort 2 and 3: Day 28, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
    Measure Participants 21 19 20 17 9 24
    Least Squares Mean (95% Confidence Interval) [mmol/L]
    0.321
    -1.043
    -2.900
    -1.240
    -2.154
    1.627
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo - Period 1, Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.680
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -1.306
    Confidence Interval (2-Sided) 95%
    -7.565 to 4.953
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cohort 1: LUM 200 mg qd - Period 1, Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.409
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -2.670
    Confidence Interval (2-Sided) 95%
    -9.053 to 3.712
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo - Period 2, Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.161
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -4.526
    Confidence Interval (2-Sided) 95%
    -10.888 to 1.835
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2, Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.396
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -2.867
    Confidence Interval (2-Sided) 95%
    -9.543 to 3.810
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2, Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.365
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value -3.780
    Confidence Interval (2-Sided) 95%
    -12.028 to 4.467
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Primary Outcome
    Title Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56
    Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.
    Time Frame Cohort 4: Baseline, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Measure Participants 60 55
    Least Squares Mean (Standard Error) [percent predicted of FEV1]
    -1.23
    (0.801)
    -0.62
    (0.829)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cohort 1: Placebo - Period 1, Cohort 1: LUM 200 mg qd - Period 1
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5978
    Comments
    Method Mixed Model Repeated Measure (MMRM)
    Comments
    Method of Estimation Estimation Parameter LS Mean difference
    Estimated Value 0.60
    Confidence Interval (2-Sided) 95%
    -1.66 to 2.86
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14
    Description
    Time Frame Cohort 1: Baseline, Day 14

    Outcome Measure Data

    Analysis Population Description
    Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 1: LUM 200 mg qd - Period 1 Cohort 1: Placebo - Period 1
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14). Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 14).
    Measure Participants 36 17
    Least Squares Mean (95% Confidence Interval) [mmol/L]
    -4.442
    -1.668
    8. Secondary Outcome
    Title Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14
    Description
    Time Frame Cohort 2: Baseline, Day 14

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2: LUM 200 mg qd - Period 1 Cohort 2: LUM 400 mg qd - Period 1 Cohort 2: LUM 600 mg qd (HO) - Period 1 Cohort 2: LUM 600 mg qd (HE) - Period 1 Cohort 3: LUM 400 mg q12h - Period 1 Cohort 2 and 3: Placebo (HO and HE) - Period 1
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28). Participants heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28).
    Measure Participants 19 17 21 17 11 25
    Least Squares Mean (95% Confidence Interval) [mmol/L]
    -6.490
    -5.901
    -9.442
    -3.137
    -9.179
    0.048
    9. Secondary Outcome
    Title Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56
    Description
    Time Frame Cohort 4: Baseline, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Measure Participants 59 54
    Least Squares Mean (Standard Error) [mmol/L]
    -0.78
    (1.230)
    -11.82
    (1.281)
    10. Secondary Outcome
    Title Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21
    Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
    Time Frame Cohort 1: Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 Cohort 1: Placebo - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21).
    Measure Participants 20 18 21
    Least Squares Mean (95% Confidence Interval) [liters]
    0.128
    0.015
    -0.046
    11. Secondary Outcome
    Title Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21
    Description FEV1 and ppFEV1 are defined in Outcome Measure 6.
    Time Frame Cohort 1: Day 14, Day 21

    Outcome Measure Data

    Analysis Population Description
    Cohort 1 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 1. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 Cohort 1: Placebo - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21).
    Measure Participants 20 18 21
    Least Squares Mean (95% Confidence Interval) [percent predicted of FEV1]
    3.46
    0.63
    -1.44
    12. Secondary Outcome
    Title Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56
    Description FEV1 and ppFEV1 are defined in Outcome Measure 6.
    Time Frame Cohort 2 and 3: Day 28, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
    Measure Participants 21 20 20 17 10 27
    Least Squares Mean (95% Confidence Interval) [percent predicted of FEV1]
    1.96
    1.99
    6.15
    2.29
    6.09
    -1.57
    13. Secondary Outcome
    Title Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56
    Description FEV1 and ppFEV1 are defined in Outcome Measure 6.
    Time Frame Cohort 2 and 3: Day 28, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
    Measure Participants 21 20 20 17 10 24
    Least Squares Mean (95% Confidence Interval) [percent change]
    3.13
    2.98
    9.70
    4.30
    8.24
    -2.05
    14. Secondary Outcome
    Title Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56
    Description FEV1 and ppFEV1 are defined in Outcome Measure 6.
    Time Frame Cohort 2 and 3: Baseline, Day 28 and 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Here, n = participants evaluable for specified category for each arm, respectively. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HE) Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) Cohort 2 and 3: Placebo (HO and HE)
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous (HE) for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
    Measure Participants 23 21 21 21 11 27
    Day 28: (n= 21, 20, 20, 18, 11, 27)
    0.21
    -1.35
    -2.62
    -3.82
    -4.52
    -0.03
    Day 56: (n= 21, 20, 20, 17, 10, 24)
    1.82
    0.64
    3.59
    -1.68
    2.16
    -2.02
    15. Secondary Outcome
    Title Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56
    Description FEV1 and ppFEV1 are defined in Outcome Measure 6.
    Time Frame Cohort 2 and 3: Baseline, Day 28 and 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Here, n = participants evaluable for specified category for each arm, respectively. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2: LUM 200 mg qd/LUM 200 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 400 mg qd/LUM 400 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HO) Cohort 2: LUM 600 mg qd/LUM 600 mg qd+IVA 250 mg q12h (HE) Cohort 3: LUM 400 mg q12h/LUM 400 mg q12h+IVA 250 mg q12h (HO) Cohort 2 and 3: Placebo (HO and HE)
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous (HE) for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28), followed by 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28), followed by 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28), followed by lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
    Measure Participants 23 21 21 21 11 27
    Day 28: (n= 21, 20, 20, 18, 11, 27)
    0.24
    -1.15
    -3.13
    -5.46
    -6.39
    1.89
    Day 56: (n= 21, 20, 20, 17, 10, 24)
    2.51
    1.72
    5.55
    -2.34
    2.96
    -2.42
    16. Secondary Outcome
    Title Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56
    Description FEV1 and ppFEV1 are defined in Outcome Measure 6.
    Time Frame Cohort 4: Baseline, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Measure Participants 60 55
    Least Squares Mean (Standard Error) [percent change]
    -2.20
    (1.373)
    -0.69
    (1.423)
    17. Secondary Outcome
    Title Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56
    Description The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
    Time Frame Cohort 2 and 3: Day 28, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 2 and 3 Full Analysis Set included all randomized participants who received at least 1 dose of study drug in Cohort 2 or 3. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56).
    Measure Participants 21 20 20 17 10 25
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    3.3
    7.9
    8.9
    5.5
    11.2
    -8.6
    18. Secondary Outcome
    Title Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56
    Description CFQ-R respiratory domain is defined in Outcome Measure 17.
    Time Frame Cohort 4: Baseline, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Measure Participants 60 55
    Least Squares Mean (Standard Error) [units on a scale]
    -0.82
    (1.802)
    5.66
    (1.864)
    19. Secondary Outcome
    Title Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56
    Description BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).
    Time Frame Cohort 4: Baseline, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Measure Participants 60 56
    Least Squares Mean (Standard Error) [kg/m^2]
    0.08
    (0.075)
    -0.04
    (0.077)
    20. Secondary Outcome
    Title Cohort 4: Absolute Change From Baseline in Weight at Day 56
    Description
    Time Frame Cohort 4: Baseline, Day 56

    Outcome Measure Data

    Analysis Population Description
    Cohort 4 Full Analysis Set included all randomized participants who received any amount of study drug in Cohort 4. Number of participants analysed signifies participants evaluable for this outcome.
    Arm/Group Title Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    Measure Participants 60 56
    Least Squares Mean (Standard Error) [kg]
    0.16
    (0.211)
    -0.11
    (0.216)

    Adverse Events

    Time Frame Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21); Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56); Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1: LUM 200 mg qd - Period 1 Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 Cohort 1: Placebo - Period 1 Cohort 1: Placebo - Period 2 Cohort 2: LUM 200 mg qd - Period 1 Cohort 2: LUM 400 mg qd - Period 1 Cohort 2: LUM 600 mg qd - Period 1 Cohort 3: LUM 400 mg q12h - Period 1 Cohort 2 and 3: Placebo (HO and HE) - Period 1 Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO&HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2 Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Arm/Group Description Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 14). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 150 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 14). Participants homozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd in combination with ivacaftor matched placebo q12h (Day 15 through Day 21). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor alone qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor alone q12h (Day 1 through Day 28). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo qd (Day 1 through Day 28). Participants homozygous for the F508del-CFTR mutation received 200 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received 600 mg of lumacaftor qd in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 29 through Day 56). Participants homozygous or heterozygous for the F508del-CFTR mutation received lumacaftor matched placebo in combination with ivacaftor matched placebo q12h (Day 29 through Day 56). Participants heterozygous for the F508del-CFTR mutation received lumacaftor in combination with ivacaftor matched placebo q12h (Day 1 through Day 56). Participants heterozygous for the F508del-CFTR mutation received 400 mg of lumacaftor q12h in combination with 250 mg of ivacaftor q12h (Day 1 through Day 56).
    All Cause Mortality
    Cohort 1: LUM 200 mg qd - Period 1 Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 Cohort 1: Placebo - Period 1 Cohort 1: Placebo - Period 2 Cohort 2: LUM 200 mg qd - Period 1 Cohort 2: LUM 400 mg qd - Period 1 Cohort 2: LUM 600 mg qd - Period 1 Cohort 3: LUM 400 mg q12h - Period 1 Cohort 2 and 3: Placebo (HO and HE) - Period 1 Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO&HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2 Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Cohort 1: LUM 200 mg qd - Period 1 Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 Cohort 1: Placebo - Period 1 Cohort 1: Placebo - Period 2 Cohort 2: LUM 200 mg qd - Period 1 Cohort 2: LUM 400 mg qd - Period 1 Cohort 2: LUM 600 mg qd - Period 1 Cohort 3: LUM 400 mg q12h - Period 1 Cohort 2 and 3: Placebo (HO and HE) - Period 1 Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO&HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2 Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/41 (0%) 0/20 (0%) 0/20 (0%) 0/21 (0%) 0/21 (0%) 2/23 (8.7%) 0/21 (0%) 3/42 (7.1%) 2/11 (18.2%) 1/27 (3.7%) 0/21 (0%) 1/20 (5%) 4/38 (10.5%) 1/11 (9.1%) 4/27 (14.8%) 5/63 (7.9%) 9/62 (14.5%)
    Congenital, familial and genetic disorders
    CYSTIC FIBROSIS LUNG 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 1/42 (2.4%) 1 1/11 (9.1%) 1 1/27 (3.7%) 1 0/21 (0%) 0 1/20 (5%) 1 3/38 (7.9%) 3 1/11 (9.1%) 1 4/27 (14.8%) 4 0/63 (0%) 0 0/62 (0%) 0
    Immune system disorders
    HYPERSENSITIVITY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Infections and infestations
    Infective pulmonary exacerbation of cystic fibrosis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 3/63 (4.8%) 4 7/62 (11.3%) 7
    PNEUMONIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Investigations
    Spirometry abnormal 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    BLOOD CREATINE PHOSPHOKINASE INCREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Renal and urinary disorders
    Nephrolithiasis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 1/63 (1.6%) 1 0/62 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 1/27 (3.7%) 1 1/63 (1.6%) 1 1/62 (1.6%) 1
    DYSPNOEA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    RESPIRATION ABNORMAL 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Other (Not Including Serious) Adverse Events
    Cohort 1: LUM 200 mg qd - Period 1 Cohort 1: LUM 200 mg qd+IVA 150 mg q12h - Period 2 Cohort 1: LUM 200 mg qd+IVA 250 mg q12h - Period 2 Cohort 1: Placebo - Period 1 Cohort 1: Placebo - Period 2 Cohort 2: LUM 200 mg qd - Period 1 Cohort 2: LUM 400 mg qd - Period 1 Cohort 2: LUM 600 mg qd - Period 1 Cohort 3: LUM 400 mg q12h - Period 1 Cohort 2 and 3: Placebo (HO and HE) - Period 1 Cohort 2: LUM 200 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 400 mg qd+IVA 250 mg q12h (HO) - Period 2 Cohort 2: LUM 600 mg qd+IVA 250 mg q12h (HO&HE) - Period 2 Cohort 3: LUM 400 mg q12h+IVA 250 mg q12h (HO) - Period 2 Cohort 2 and 3: Placebo (HO and HE) - Period 2 Cohort 4: Placebo Cohort 4: LUM 400 mg q12h+IVA 250 mg q12h
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 29/41 (70.7%) 14/20 (70%) 12/20 (60%) 12/21 (57.1%) 15/21 (71.4%) 17/23 (73.9%) 18/21 (85.7%) 37/42 (88.1%) 6/11 (54.5%) 23/27 (85.2%) 12/21 (57.1%) 15/20 (75%) 26/38 (68.4%) 10/11 (90.9%) 20/27 (74.1%) 53/63 (84.1%) 51/62 (82.3%)
    Blood and lymphatic system disorders
    LYMPHADENOPATHY 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Eosinophilia 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Increased tendency to bruise 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Leukopenia 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Cardiac disorders
    SINUS BRADYCARDIA 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Tachycardia 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Congenital, familial and genetic disorders
    CYSTIC FIBROSIS LUNG 2/41 (4.9%) 2 2/20 (10%) 2 1/20 (5%) 1 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 2/21 (9.5%) 2 7/42 (16.7%) 7 1/11 (9.1%) 1 2/27 (7.4%) 2 1/21 (4.8%) 1 1/20 (5%) 1 3/38 (7.9%) 3 1/11 (9.1%) 1 4/27 (14.8%) 4 1/63 (1.6%) 1 0/62 (0%) 0
    Cystic fibrosis related diabetes 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Ear and labyrinth disorders
    EAR PAIN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    EAR DISCOMFORT 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    EAR DISORDER 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    TINNITUS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 2 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Vertigo 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 3 0/62 (0%) 0
    Eye disorders
    EYELID OEDEMA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    CONJUNCTIVITIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Vision Blurred 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Gastrointestinal disorders
    DIARRHOEA 1/41 (2.4%) 1 1/20 (5%) 1 1/20 (5%) 1 0/21 (0%) 0 2/21 (9.5%) 2 1/23 (4.3%) 1 3/21 (14.3%) 3 5/42 (11.9%) 5 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 2/20 (10%) 2 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 5/63 (7.9%) 9 7/62 (11.3%) 7
    ABDOMINAL PAIN UPPER 3/41 (7.3%) 3 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 2/23 (8.7%) 2 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 2/27 (7.4%) 2 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 1/11 (9.1%) 1 2/27 (7.4%) 2 7/63 (11.1%) 10 5/62 (8.1%) 5
    ABDOMINAL DISCOMFORT 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 2/21 (9.5%) 2 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    ABDOMINAL PAIN 1/41 (2.4%) 2 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 2/21 (9.5%) 3 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 1/20 (5%) 1 2/38 (5.3%) 2 0/11 (0%) 0 1/27 (3.7%) 1 3/63 (4.8%) 5 1/62 (1.6%) 1
    NAUSEA 2/41 (4.9%) 2 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 3 8/42 (19%) 8 1/11 (9.1%) 1 3/27 (11.1%) 3 0/21 (0%) 0 1/20 (5%) 2 3/38 (7.9%) 3 0/11 (0%) 0 2/27 (7.4%) 2 7/63 (11.1%) 9 7/62 (11.3%) 7
    VOMITING 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 1/21 (4.8%) 2 2/42 (4.8%) 2 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 2/20 (10%) 2 2/38 (5.3%) 2 0/11 (0%) 0 1/27 (3.7%) 1 2/63 (3.2%) 2 4/62 (6.5%) 4
    ABDOMINAL DISTENSION 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    ABDOMINAL PAIN LOWER 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    FLATULENCE 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 3/21 (14.3%) 3 3/42 (7.1%) 3 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    GASTROOESOPHAGEAL REFLUX DISEASE 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 2/27 (7.4%) 2 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 5/62 (8.1%) 7
    HYPOAESTHESIA ORAL 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    CONSTIPATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 2/38 (5.3%) 2 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    DISTAL ILEAL OBSTRUCTION SYNDROME 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    DRY MOUTH 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    DYSPEPSIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 3/62 (4.8%) 3
    RECTAL HAEMORRHAGE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    TOOTHACHE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    FREQUENT BOWEL MOVEMENTS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 2/62 (3.2%) 3
    FAECAL VOLUME INCREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    DYSPHAGIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    LIP SWELLING 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    POST-TUSSIVE VOMITING 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    STEATORRHOEA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    General disorders
    FATIGUE 1/41 (2.4%) 1 1/20 (5%) 1 0/20 (0%) 0 1/21 (4.8%) 1 3/21 (14.3%) 3 0/23 (0%) 0 1/21 (4.8%) 1 3/42 (7.1%) 4 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 1/20 (5%) 1 1/38 (2.6%) 1 0/11 (0%) 0 1/27 (3.7%) 1 6/63 (9.5%) 6 4/62 (6.5%) 6
    PYREXIA 3/41 (7.3%) 3 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 6/42 (14.3%) 7 0/11 (0%) 0 3/27 (11.1%) 4 0/21 (0%) 0 1/20 (5%) 1 1/38 (2.6%) 1 0/11 (0%) 0 1/27 (3.7%) 1 9/63 (14.3%) 10 7/62 (11.3%) 7
    PAIN 3/41 (7.3%) 3 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 3/63 (4.8%) 3 0/62 (0%) 0
    APPLICATION SITE PRURITUS 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    CATHETER SITE HAEMORRHAGE 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    CATHETER SITE PAIN 1/41 (2.4%) 1 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    CHEST DISCOMFORT 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    CHILLS 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 3 0/62 (0%) 0
    FEELING HOT 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 4 0/62 (0%) 0
    INJECTION SITE HAEMORRHAGE 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Chest pain 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Exercise tolerance decreased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Malaise 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Vessel puncture site bruise 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    NON-CARDIAC CHEST PAIN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 2 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    APPLICATION SITE IRRITATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    FEELING OF BODY TEMPERATURE CHANGE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 2 0/63 (0%) 0 0/62 (0%) 0
    INFLUENZA LIKE ILLNESS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Hepatobiliary disorders
    Hepatomegaly 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    Immune system disorders
    Seasonal allergy 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 1/27 (3.7%) 1 1/63 (1.6%) 1 0/62 (0%) 0
    Infections and infestations
    VIRAL INFECTION 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    RHINITIS 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    UPPER RESPIRATORY TRACT INFECTION 0/41 (0%) 0 2/20 (10%) 2 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 5/23 (21.7%) 5 1/21 (4.8%) 1 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 3/21 (14.3%) 3 2/20 (10%) 2 3/38 (7.9%) 3 1/11 (9.1%) 1 4/27 (14.8%) 4 3/63 (4.8%) 4 3/62 (4.8%) 3
    BACTERIAL DISEASE CARRIER 0/41 (0%) 0 1/20 (5%) 2 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    CANDIDIASIS 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    GASTROENTERITIS 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    ORAL HERPES 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    VIRAL UPPER RESPIRATORY TRACT INFECTION 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 2/42 (4.8%) 2 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 4/63 (6.3%) 4 2/62 (3.2%) 2
    Infective pulmonary exacerbation of cystic fibrosis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 10/63 (15.9%) 11 7/62 (11.3%) 8
    NASOPHARYNGITIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 6/63 (9.5%) 6 2/62 (3.2%) 2
    ORAL CANDIDIASIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 2/62 (3.2%) 2
    PHARYNGITIS STREPTOCOCCAL 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 0/62 (0%) 0
    Rash pustular 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 2/62 (3.2%) 2
    Acute sinusitis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Bronchitis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Bronchopulmonary aspergillosis allergic 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    INFLUENZA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Conjunctivitis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Gastroenteritis viral 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Kidney infection 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Lower respiratory tract infection bacterial 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Lung infection 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Upper respiratory tract infection bacterial 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Vulvovaginal mycotic infection 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    SINUSITIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 1/21 (4.8%) 1 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    FUNGAL INFECTION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    HERPES SIMPLEX 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    LARYNGITIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    OTITIS MEDIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PHARYNGITIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    RHINOVIRUS INFECTION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    URINARY TRACT INFECTION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    VIRAL RASH 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Injury, poisoning and procedural complications
    CHEST INJURY 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    EXCORIATION 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    JOINT SPRAIN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    LIMB INJURY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MUSCLE STRAIN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    THERMAL BURN 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Ligament sprain 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 0/62 (0%) 0
    Procedural pain 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    Arthropod sting 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    JOINT INJURY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Contusion 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 2/38 (5.3%) 2 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Rib fracture 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Road traffic accident 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    SUNBURN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    VERTEBRAL INJURY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Animal bite 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    ARTHROPOD BITE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Investigations
    BLOOD GLUCOSE INCREASED 1/41 (2.4%) 1 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    C-REACTIVE PROTEIN INCREASED 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 5/42 (11.9%) 5 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 5/63 (7.9%) 6 2/62 (3.2%) 2
    GLUCOSE URINE PRESENT 0/41 (0%) 0 1/20 (5%) 1 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    LIVER FUNCTION TEST ABNORMAL 2/41 (4.9%) 2 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 2/23 (8.7%) 2 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    PROTHROMBIN TIME PROLONGED 1/41 (2.4%) 1 2/20 (10%) 2 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PULMONARY FUNCTION TEST DECREASED 2/41 (4.9%) 2 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 2/11 (18.2%) 2 0/27 (0%) 0 2/63 (3.2%) 2 2/62 (3.2%) 3
    ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    ALANINE AMINOTRANSFERASE INCREASED 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 4/62 (6.5%) 4
    BLOOD IMMUNOGLOBULIN E INCREASED 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BLOOD SODIUM DECREASED 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BLOOD URINE PRESENT 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    HEPATIC ENZYME INCREASED 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 1/63 (1.6%) 1 0/62 (0%) 0
    INTERNATIONAL NORMALISED RATIO INCREASED 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Forced expiratory volume decreased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 4/63 (6.3%) 4 4/62 (6.5%) 4
    Aspartate aminotransferase increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 4/62 (6.5%) 4
    Blood creatine phosphokinase increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 2/42 (4.8%) 2 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 2/38 (5.3%) 2 1/11 (9.1%) 1 1/27 (3.7%) 1 0/63 (0%) 0 3/62 (4.8%) 3
    Sputum abnormal 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    Blood alkaline phosphatase increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Blood creatinine decreased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Blood creatinine increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Blood immunoglobulin G increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Blood lactate dehydrogenase increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Chest X-ray abnormal 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Eosinophil count increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Gamma-glutamyltransferase increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Interleukin level increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 2/27 (7.4%) 3 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Protein total increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Transaminases increased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Weight decreased 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 1/42 (2.4%) 1 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    WHITE BLOOD CELL COUNT INCREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BLOOD GLUCOSE DECREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    NEUTROPHIL COUNT INCREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BACTERIA URINE IDENTIFIED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BLOOD PHOSPHORUS DECREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BLOOD POTASSIUM INCREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    CULTURE THROAT POSITIVE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    ELECTROCARDIOGRAM QT PROLONGED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    FUNGUS SPUTUM TEST POSITIVE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PLATELET COUNT DECREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PROTEIN URINE PRESENT 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    URINE KETONE BODY PRESENT 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    WHITE BLOOD CELLS URINE POSITIVE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Metabolism and nutrition disorders
    HYPOGLYCAEMIA 1/41 (2.4%) 1 1/20 (5%) 1 0/20 (0%) 0 1/21 (4.8%) 1 2/21 (9.5%) 3 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 1/21 (4.8%) 1 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    DEHYDRATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Decreased appetite 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 1/42 (2.4%) 1 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 2/11 (18.2%) 2 0/27 (0%) 0 4/63 (6.3%) 4 0/62 (0%) 0
    ANOREXIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    HYPERCALCAEMIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    HYPERGLYCAEMIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 1/21 (4.8%) 2 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    MUSCULOSKELETAL CHEST PAIN 0/41 (0%) 0 1/20 (5%) 1 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 2/38 (5.3%) 6 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    PAIN IN EXTREMITY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MUSCLE SPASMS 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 2/27 (7.4%) 2 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MYALGIA 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 2/42 (4.8%) 2 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Arthritis 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 3
    Clubbing 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Musculoskeletal pain 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 2/21 (9.5%) 2 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Osteopenia 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    MUSCULOSKELETAL DISCOMFORT 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    COSTOCHONDRITIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MEDIAL TIBIAL STRESS SYNDROME 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MUSCLE TIGHTNESS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MUSCULOSKELETAL STIFFNESS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    NECK PAIN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    TORTICOLLIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Back pain 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 2/38 (5.3%) 2 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    Nervous system disorders
    DIZZINESS 0/41 (0%) 0 2/20 (10%) 2 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 2/38 (5.3%) 2 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 2/62 (3.2%) 2
    SINUS HEADACHE 1/41 (2.4%) 1 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 1/62 (1.6%) 1
    MIGRAINE 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 3 0/63 (0%) 0 0/62 (0%) 0
    TREMOR 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    TUNNEL VISION 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    HEADACHE 4/41 (9.8%) 4 0/20 (0%) 0 1/20 (5%) 1 4/21 (19%) 5 5/21 (23.8%) 7 1/23 (4.3%) 1 4/21 (19%) 4 4/42 (9.5%) 7 1/11 (9.1%) 2 5/27 (18.5%) 9 0/21 (0%) 0 2/20 (10%) 2 7/38 (18.4%) 10 2/11 (18.2%) 3 5/27 (18.5%) 7 11/63 (17.5%) 18 3/62 (4.8%) 4
    NEURALGIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PRESYNCOPE 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    LETHARGY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 0/62 (0%) 0
    DYSGEUSIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Psychiatric disorders
    ANXIETY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    INSOMNIA 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/21 (9.5%) 2 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    MOOD SWINGS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    DEPRESSED MOOD 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    Abnormal dreams 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 2
    Renal and urinary disorders
    PYURIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Chromaturia 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Renal failure acute 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    DYSURIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PROTEINURIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Reproductive system and breast disorders
    DYSMENORRHOEA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 1/62 (1.6%) 1
    MENSTRUATION DELAYED 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BREAST TENDERNESS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MENOMETRORRHAGIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MENORRHAGIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    MENSTRUAL DISORDER 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Dysmenorrhoea 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 1/62 (1.6%) 1
    Vulvovaginal burning sensation 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Vulvovaginal discomfort 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Respiratory, thoracic and mediastinal disorders
    COUGH 6/41 (14.6%) 6 4/20 (20%) 5 1/20 (5%) 1 1/21 (4.8%) 1 4/21 (19%) 4 3/23 (13%) 3 8/21 (38.1%) 8 12/42 (28.6%) 13 1/11 (9.1%) 1 6/27 (22.2%) 6 3/21 (14.3%) 5 5/20 (25%) 5 5/38 (13.2%) 6 3/11 (27.3%) 4 6/27 (22.2%) 6 12/63 (19%) 15 13/62 (21%) 16
    PRODUCTIVE COUGH 3/41 (7.3%) 3 1/20 (5%) 1 0/20 (0%) 0 2/21 (9.5%) 2 3/21 (14.3%) 3 2/23 (8.7%) 2 2/21 (9.5%) 2 6/42 (14.3%) 7 2/11 (18.2%) 2 5/27 (18.5%) 5 2/21 (9.5%) 3 1/20 (5%) 1 1/38 (2.6%) 1 2/11 (18.2%) 2 1/27 (3.7%) 1 3/63 (4.8%) 4 3/62 (4.8%) 3
    OROPHARYNGEAL PAIN 2/41 (4.9%) 2 1/20 (5%) 1 2/20 (10%) 2 0/21 (0%) 0 2/21 (9.5%) 2 2/23 (8.7%) 2 0/21 (0%) 0 1/42 (2.4%) 1 1/11 (9.1%) 1 1/27 (3.7%) 1 1/21 (4.8%) 1 4/20 (20%) 5 0/38 (0%) 0 2/11 (18.2%) 2 1/27 (3.7%) 1 5/63 (7.9%) 6 3/62 (4.8%) 3
    NASAL CONGESTION 0/41 (0%) 0 1/20 (5%) 1 3/20 (15%) 3 0/21 (0%) 0 2/21 (9.5%) 2 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 3/27 (11.1%) 3 2/21 (9.5%) 2 3/20 (15%) 3 2/38 (5.3%) 2 0/11 (0%) 0 1/27 (3.7%) 1 4/63 (6.3%) 5 5/62 (8.1%) 7
    RHINORRHOEA 2/41 (4.9%) 2 1/20 (5%) 1 1/20 (5%) 1 2/21 (9.5%) 2 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 3/27 (11.1%) 3 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 1/11 (9.1%) 1 1/27 (3.7%) 1 3/63 (4.8%) 4 4/62 (6.5%) 4
    DYSPNOEA 3/41 (7.3%) 3 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 10/42 (23.8%) 10 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 4/63 (6.3%) 5 9/62 (14.5%) 10
    RALES 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 3/21 (14.3%) 4 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 2/63 (3.2%) 2 2/62 (3.2%) 2
    RESPIRATION ABNORMAL 1/41 (2.4%) 1 0/20 (0%) 0 1/20 (5%) 1 1/21 (4.8%) 1 1/21 (4.8%) 1 0/23 (0%) 0 2/21 (9.5%) 2 7/42 (16.7%) 8 2/11 (18.2%) 2 0/27 (0%) 0 1/21 (4.8%) 2 0/20 (0%) 0 2/38 (5.3%) 2 0/11 (0%) 0 0/27 (0%) 0 9/63 (14.3%) 9 17/62 (27.4%) 20
    WHEEZING 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 2/21 (9.5%) 2 2/21 (9.5%) 2 0/23 (0%) 0 2/21 (9.5%) 2 1/42 (2.4%) 1 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 2/38 (5.3%) 2 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    LUNG HYPERINFLATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 3/21 (14.3%) 3 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    RESPIRATORY TRACT CONGESTION 0/41 (0%) 0 1/20 (5%) 1 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 2/27 (7.4%) 2 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 1/11 (9.1%) 1 0/27 (0%) 0 6/63 (9.5%) 6 5/62 (8.1%) 6
    BRONCHIAL SECRETION RETENTION 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    HYPOVENTILATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    INCREASED VISCOSITY OF BRONCHIAL SECRETION 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    NASAL MUCOSAL DISORDER 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    NASAL OEDEMA 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    OBSTRUCTIVE AIRWAYS DISORDER 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PROLONGED EXPIRATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    RHINITIS ALLERGIC 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 1/21 (4.8%) 1 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    RHONCHI 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    SINUS CONGESTION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 1/23 (4.3%) 1 0/21 (0%) 0 3/42 (7.1%) 3 0/11 (0%) 0 2/27 (7.4%) 2 0/21 (0%) 0 1/20 (5%) 2 0/38 (0%) 0 2/11 (18.2%) 2 2/27 (7.4%) 2 4/63 (6.3%) 4 0/62 (0%) 0
    SINUS DISORDER 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    SNEEZING 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 1/63 (1.6%) 1 1/62 (1.6%) 1
    HAEMOPTYSIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 4/23 (17.4%) 4 3/21 (14.3%) 3 2/42 (4.8%) 2 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 3/38 (7.9%) 3 0/11 (0%) 0 2/27 (7.4%) 2 7/63 (11.1%) 10 5/62 (8.1%) 5
    PLEURITIC PAIN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 3/27 (11.1%) 3 0/63 (0%) 0 0/62 (0%) 0
    EPISTAXIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 1/63 (1.6%) 1 1/62 (1.6%) 1
    PARANASAL SINUS HYPERSECRETION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 1/62 (1.6%) 1
    SPUTUM DISCOLOURED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    OBSTRUCTIVE AIRWAYS DISORDER 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 1/23 (4.3%) 1 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    BRONCHOSPASM 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    DYSPHONIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    DYSPNOEA EXERTIONAL 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    NASAL INFLAMMATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PAINFUL RESPIRATION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    PULMONARY CONGESTION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    SPUTUM INCREASED 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 12/63 (19%) 12 10/62 (16.1%) 10
    UPPER-AIRWAY COUGH SYNDROME 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 3/62 (4.8%) 3
    BRONCHIAL OBSTRUCTION 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    HICCUPS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    NASAL DRYNESS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    PHARYNGEAL OEDEMA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    PLEURISY 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    PULMONARY PAIN 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Skin and subcutaneous tissue disorders
    RASH MACULAR 2/41 (4.9%) 3 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    RASH PAPULAR 1/41 (2.4%) 1 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    ACNE 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    DERMATITIS CONTACT 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    HYPERHIDROSIS 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    HYPOAESTHESIA FACIAL 0/41 (0%) 0 1/20 (5%) 1 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    NIGHT SWEATS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 1/21 (4.8%) 1 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 1/62 (1.6%) 1
    PRURITUS 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 1/21 (4.8%) 1 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 1/38 (2.6%) 1 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    RASH FOLLICULAR 1/41 (2.4%) 1 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    RASH MACULO-PAPULAR 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    URTICARIA 0/41 (0%) 0 0/20 (0%) 0 1/20 (5%) 1 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 1/27 (3.7%) 1 0/63 (0%) 0 0/62 (0%) 0
    Dermatitis atopic 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    Erythema 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 1/63 (1.6%) 1 0/62 (0%) 0
    Rash generalised 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1
    RASH 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 2/23 (8.7%) 2 1/21 (4.8%) 1 3/42 (7.1%) 3 0/11 (0%) 0 0/27 (0%) 0 1/21 (4.8%) 1 0/20 (0%) 0 1/38 (2.6%) 1 1/11 (9.1%) 1 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    ALOPECIA 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 1/42 (2.4%) 1 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    ECCHYMOSIS 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 1/20 (5%) 1 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 0/62 (0%) 0
    Vascular disorders
    Hot flush 0/41 (0%) 0 0/20 (0%) 0 0/20 (0%) 0 0/21 (0%) 0 0/21 (0%) 0 0/23 (0%) 0 0/21 (0%) 0 0/42 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/21 (0%) 0 0/20 (0%) 0 0/38 (0%) 0 0/11 (0%) 0 0/27 (0%) 0 0/63 (0%) 0 1/62 (1.6%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.

    Results Point of Contact

    Name/Title Medical Monitor
    Organization Vertex Pharmaceuticals Incorporated
    Phone 617-341-6777
    Email medicalinfo@vrtx.com
    Responsible Party:
    Vertex Pharmaceuticals Incorporated
    ClinicalTrials.gov Identifier:
    NCT01225211
    Other Study ID Numbers:
    • VX09-809-102
    • 2010-020413-90
    First Posted:
    Oct 20, 2010
    Last Update Posted:
    Oct 5, 2015
    Last Verified:
    Sep 1, 2015