Asthma, COPD
Conditions
Brief summary
This study is a Phase IIa, randomized, placebo-controlled, double-blind, 2-way crossover, 2-center (conducted in EU; The Netherlands) study in male and female subjects with stable, mild HDM-allergic asthma.
Detailed description
This study is a Phase IIa, randomized, placebo-controlled, double-blind, 2-way crossover, 2-center (conducted in EU; The Netherlands) study in male and female subjects with stable, mild HDM-allergic asthma. The study will consist of two identical study periods of 12 treatment days each, separated by a washout period of at least 3 weeks (and no more than 7 weeks). Approximately 36 eligible subjects will be enrolled, to yield 32 evaluable subjects who will be treated with both FP-025 (400 mg BID) or matching placebo in a cross-over design from the evening of Day 1 till the morning of Day 12 (22 doses per study period in total).
Interventions
DRUGFP-025 capsules
FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days.
DRUGPlacebo FP-025 capsules
Placebo FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days.
Sponsors
Foresee Pharmaceuticals Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
The following criteria must be met by all subjects considered for study participation: 1. Females or males, between 18 and 55 years of age at Screening, inclusive, on the day of signing the Informed Consent Form (ICF). 2. Apart from a clinically stable asthma and HDM-allergy, subjects should be generally healthy with no history of a clinically relevant medical condition that in the opinion of the investigator might interfere with successful study conduct and no clinically relevant abnormalities on medical history, physical exam, vital signs, laboratory parameters or ECG at Screening. 3. Subject has a BMI ≥ 18.0 kg/m2 and ≤ 32.0 kg/m2 (and weighs ≥50 kg). 4. Subjects have been diagnosed with asthma cf GINA guidelines. 5. Subjects should have established allergy for HDM (serum HDM-specific IgE or positive SPT at Screening or documented within 1 year pre-screening). 6. No severe exacerbation of asthma within past 1 year requiring hospital admission and/or treatment with oral corticosteroids; no (never) intensive care admissions for asthma or intubation). 7. FEV1 should be ≥70% of predicted on Screening Day 2. 8. On Screening Day 2, PC20FEV1(Meth) should be \<16 mg/mL if methacholine chloride is used (or adjusted by a factor of 1.2 if methacholine bromide is used). 9. Baseline blood eosinophils should be ≥150 cells/μL at Screening or documented within 3 months before Screening Day 1. 10. Subjects should have a documented airway late response to inhaled HDM on Screening Day 3. 11. Subjects of childbearing potential must be willing to use adequate contraception (double-barrier) or must refrain from intercourse. 12. Female subjects of non-childbearing potential must have had ≥ 12 months of spontaneous amenorrhea (with folliclestimulating hormone \[FSH\] ≥ 30 mIU/mL). Surgically sterile women are defined as those who have had a hysterectomy, bilateral ovariectomy (for 'benign' reasons), or bilateral tubal ligation. 13. All female subjects should have a negative pregnancy test at Screening and on Day -1. 14. Negative alcohol breath test on Screening Day 1 and Day -1. 15. Negative cotinine test on Screening Day 1 and Day -1. 16. Negative urine drug screen for recreational and other drugs on Screening Day 1 and Day -1. 17. Subjects are non-smokers. A non-smoker is defined as an individual who has abstained from smoking for at least 1 year prior to Screening Day 1. Number of years smoked x number of packs per day should be \<5 pack years. 18. Subject should be willing and able to perform the lung function tests and other study-related procedures and comply with study protocol requirements. 19. Subject should provide a signed and dated informed consent.
Exclusion criteria
Subjects will be excluded if they meet any of the following criteria: 1. Subject has any active and/or chronic (physical or mental) condition requiring maintenance (pharmaco)therapy or which otherwise precludes subject from safe or adequate study participation (ineligibility will be assessed by the PI). 2. Subject has a history of cancer (exception: localized basalioma or cervix carcinoma in situ). 3. Subject had any major (nasal) surgery in the 6 months before Screening Day 1. 4. Subject is pregnant or lactating. 5. Subject is using immunotherapy that according to the PI may interfere with the study (e.g. in case of immunotherapy with HDM or when subject is in the updosing phase of any immunotherapy). 6. Subject regularly used alcohol (intake of \>21 units/wk for males and \>14 units/wk for females) and/or recreational drugs within the last 6 months prior to screening. 7. Subject had any respiratory (viral) infections (e.g. common cold) within 3 weeks of Screening Day 1 or on Day -1. 8. Subject is using maintenance asthma therapy or long-acting bronchodilators or any other anti-asthma or anti-allergic medications (as detailed in the protocol) other than infrequent use of SABA prn only. 9. Subject is using prohibited medications as detailed in the protocol. 10. Multi-sensitized symptomatic subjects with seasonal (pollen) allergies should be included outside of the relevant allergen season and/or should not be in frequent contact with the relevant allergen during the study. 11. Subject has any known allergic response for the medications used or known severe allergic reactions or anaphylaxis (to food/medications/insect venoms). 12. Subject participated in medical studies in the past 3 months (non-biologicals) or in the past 6 months (biologicals). 13. Subject is anticipated not to comply with study medication or other aspects of the study (at the discretion of the investigator).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of FP-025 Versus Placebo on the Allergen (HDM)-Induced Late Asthmatic Response (LAR) in Subjects With Clinically Stable, Mild Allergic Asthma and Blood Eosinophilia. | FEV1 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate LAR(AUC3-8h) | Late asthmatic response (LAR) is defined as FEV1 AUC3-8h; differences between FP025 and placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Late Asthmatic Response (LAR) | FEV1 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate LAR(AUC3-8h) | Late asthmatic response (LAR) expressed as max% fall in FEV1 from post-diluent 3-8 h(LAR) baseline post allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in EAR. | FEV1 measured hourly from 0 to 3 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate EAR(AUC0-3h) | Early asthmatic response (EAR) expressed as FEV1 AUC0-3h in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma. |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Early Asthmatic Response (EAR). | FEV1 measured hourly from 0 to 3 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate maximal% fall in FEV1(0-3h) | Early asthmatic response (EAR) expressed as max% fall in FEV1 from post-diluent 0-3 h(EAR) baseline post allergen in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma. |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Joint HDM-induced Airway Response. | FEV1 measured hourly from 0 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate FEV1(AUC0-8h) | Joint HDM-induced airway response expressed as FEV1 AUC0-8h post-allergen in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma patients. |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Airway Hyper-responsiveness | PC20FEV1(Meth) or PC20FEV1(Hist) measured pre and post allergen (Day 10 versus Day12 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma | Changes in allergen-induced AHR: i.e: PC20FEV1(Meth) or PC20FEV1(Hist) pre-post allergen (Day 10 versus Day12) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma. |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 (AUC3-8 Hours) | IOS R5 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R5(AUC3-8h) | Small airway parameters measured by IOS R5(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma |
| The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 10 vs Day 12. | Blood eosinophils measured pre and post allergen (Day 10 versus Day12 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma | Changes in allergen-induced airway and systemic biomarkers (i.e. eosinophils (blood) (Day 10 versus Day12) (potential treatment effect). |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS FRES. | IOS Fres measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS Fres(AUC3-8h) | Small airway parameters measured by IOS Fres(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma |
| The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 1 vs Day 10. | Blood eosinophils measured pre allergen (Day 1 versus Day10 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma | Changes in allergen-induced airway and systemic biomarkers (i.e. eosinophils (blood) (Day 1 versus Day 10) (potential treatment effect). |
| To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10), Through Measurement of PC20FEV1. | PC20FEV1(Meth) or PC20FEV1(Hist) measured pre-allergen (Day 1 versus Day10 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma | Changes in PC20FEV1(Meth) or PC20FEV1(Hist) Day 1 versus Day 10 (potential treatment effect) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma. |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R20. | IOS R20 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R20(AUC3-8h) | Small airway parameters measured by IOS R20(AUC3-8h)) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 - R20. | IOS R5-R20 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R5-R20(AUC3-8h) | Small airway parameters measured by IOS R5-R20(AUC3-8h)) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS AX. | IOS Ax measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R5-R20(AUC3-8h) | Small airway parameters measured by IOS Ax(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma |
| Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS X5. | IOS X5 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS X5(AUC3-8h) | Small airway parameters measured by IOS X5(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma |
Other
| Measure | Time frame | Description |
|---|---|---|
| To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10) , Through Measurement of Fractionated Nitric Oxide (FeNO). | FeNO measured pre allergen (Day 1 versus Day10 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma | FeNO is measured from exhaled air by Niox Vero® device (Circassia, Oxford, United Kingdom) according to guidelines in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma. |
| To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 10 Versus Day 12), Through Measurement of Fractionated Nitric Oxide (FeNO). | FeNO measured pre and post allergen (Day 10 versus Day12 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma | FeNO is measured from exhaled air by Niox Vero® device (Circassia, Oxford, United Kingdom) according to guidelines in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FP-025 - Placebo Based on a double-blind randomized schedule, 16 subjects will receive FP-025 capsules in Period 1 and matching placebo FP-025 capsules in Period 2. Both study periods will follow the same schedule of procedures, with a washout period of at least 3 weeks and up to 7 weeks between study periods.
FP-025 capsules: FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days.
Placebo FP-025 capsules: Placebo FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days. | 13 |
| Placebo - FP-025 Based on a double-blind randomized schedule, 16 subjects will receive matching placebo FP-025 capsules in Period 1 and FP-025 capsules in Period 2. Both study periods will follow the same schedule of procedures, with a washout period of at least 3 weeks and up to 7 weeks between study periods.
FP-025 capsules: FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days.
Placebo FP-025 capsules: Placebo FP-025 capsules, BID will be administered to subjects in either Period 1 or Period 2, and given for 12 consecutive dosing days. | 14 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 1 |
| Period 1 | Lack of compliance | 0 | 1 |
| Period 2 | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | FP-025 - Placebo | Placebo - FP-025 | Total |
|---|---|---|---|
| Age, Continuous | 26.9 years STANDARD_DEVIATION 6.22 | 26.9 years STANDARD_DEVIATION 7.3 | 26.9 years STANDARD_DEVIATION 6.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 6 Participants | 11 Participants |
| FEV1 % predicted | 88.95 % predicted STANDARD_DEVIATION 8.26 | 92.04 % predicted STANDARD_DEVIATION 13.3 | 90.44 % predicted STANDARD_DEVIATION 10.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) White | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment Netherlands | 13 participants | 14 participants | 27 participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 26 |
| other Total, other adverse events | 16 / 23 | 12 / 26 |
| serious Total, serious adverse events | 0 / 23 | 0 / 26 |
Outcome results
Primary
Effect of FP-025 Versus Placebo on the Allergen (HDM)-Induced Late Asthmatic Response (LAR) in Subjects With Clinically Stable, Mild Allergic Asthma and Blood Eosinophilia.
Late asthmatic response (LAR) is defined as FEV1 AUC3-8h; differences between FP025 and placebo in subjects with clinically stable, mild allergic asthma and blood eosinophilia.
Time frame: FEV1 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate LAR(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Effect of FP-025 Versus Placebo on the Allergen (HDM)-Induced Late Asthmatic Response (LAR) in Subjects With Clinically Stable, Mild Allergic Asthma and Blood Eosinophilia. | -80.33 h*% | Standard Deviation 47.33 |
| Placebo | Effect of FP-025 Versus Placebo on the Allergen (HDM)-Induced Late Asthmatic Response (LAR) in Subjects With Clinically Stable, Mild Allergic Asthma and Blood Eosinophilia. | -113.43 h*% | Standard Deviation 48.6 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Airway Hyper-responsiveness
Changes in allergen-induced AHR: i.e: PC20FEV1(Meth) or PC20FEV1(Hist) pre-post allergen (Day 10 versus Day12) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma.
Time frame: PC20FEV1(Meth) or PC20FEV1(Hist) measured pre and post allergen (Day 10 versus Day12 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Airway Hyper-responsiveness | 0.460 mg/mL | Standard Deviation 3.4385 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Airway Hyper-responsiveness | 0.282 mg/mL | Standard Deviation 3.1754 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in EAR.
Early asthmatic response (EAR) expressed as FEV1 AUC0-3h in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma.
Time frame: FEV1 measured hourly from 0 to 3 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate EAR(AUC0-3h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in EAR. | -35.748 h*% | Standard Deviation 26.2807 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in EAR. | -28.683 h*% | Standard Deviation 25.4041 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Early Asthmatic Response (EAR).
Early asthmatic response (EAR) expressed as max% fall in FEV1 from post-diluent 0-3 h(EAR) baseline post allergen in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma.
Time frame: FEV1 measured hourly from 0 to 3 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate maximal% fall in FEV1(0-3h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Early Asthmatic Response (EAR). | -26.070 Maximal percentage fall | Standard Deviation 14.2299 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Early Asthmatic Response (EAR). | -20.294 Maximal percentage fall | Standard Deviation 14.572 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Joint HDM-induced Airway Response.
Joint HDM-induced airway response expressed as FEV1 AUC0-8h post-allergen in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma patients.
Time frame: FEV1 measured hourly from 0 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate FEV1(AUC0-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Joint HDM-induced Airway Response. | -117.543 h*% | Standard Deviation 67.4201 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Joint HDM-induced Airway Response. | -141.166 h*% | Standard Deviation 54.9937 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Late Asthmatic Response (LAR)
Late asthmatic response (LAR) expressed as max% fall in FEV1 from post-diluent 3-8 h(LAR) baseline post allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Time frame: FEV1 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate LAR(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Late Asthmatic Response (LAR) | -27.716 Maximal percentage fall | Standard Deviation 14.3153 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Late Asthmatic Response (LAR) | -36.605 Maximal percentage fall | Standard Deviation 15.0187 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS AX.
Small airway parameters measured by IOS Ax(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Time frame: IOS Ax measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R5-R20(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS AX. | 1641.804 h*% | Standard Deviation 1338.5357 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS AX. | 4446.304 h*% | Standard Deviation 6444.0241 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS FRES.
Small airway parameters measured by IOS Fres(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Time frame: IOS Fres measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS Fres(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS FRES. | 243.149 h*% | Standard Deviation 204.2451 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS FRES. | 407.199 h*% | Standard Deviation 314.7058 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R20.
Small airway parameters measured by IOS R20(AUC3-8h)) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Time frame: IOS R20 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R20(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R20. | 62.356 h*% | Standard Deviation 51.4601 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R20. | 98.653 h*% | Standard Deviation 88.7628 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 (AUC3-8 Hours)
Small airway parameters measured by IOS R5(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Time frame: IOS R5 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R5(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 (AUC3-8 Hours) | 186.438 h*% | Standard Deviation 113.2697 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 (AUC3-8 Hours) | 295.400 h*% | Standard Deviation 178.9532 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 - R20.
Small airway parameters measured by IOS R5-R20(AUC3-8h)) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Time frame: IOS R5-R20 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS R5-R20(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 17 FP-025 treated and 6 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 - R20. | 1316.841 h*% | Standard Deviation 2135.0733 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS R5 - R20. | 1120.347 h*% | Standard Deviation 339.5966 |
Secondary
Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS X5.
Small airway parameters measured by IOS X5(AUC3-8h) during LAR post-allergen challenge in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Time frame: IOS X5 measured hourly from 3 to 8 hours post dose on Day 11 During Placebo and FP-025 in Subjects with HDM-Allergic Mild Asthma with Blood Eosinophilia to generate IOS X5(AUC3-8h)
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS X5. | 403.640 h*% | Standard Deviation 237.8958 |
| Placebo | Pharmacodynamic Endpoints Include the Effect of Study Treatments on Allergen (HDM)-Induced Changes in Small Airway Parameters Following HDM-challenge, IOS X5. | 697.189 h*% | Standard Deviation 807.5676 |
Secondary
The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 10 vs Day 12.
Changes in allergen-induced airway and systemic biomarkers (i.e. eosinophils (blood) (Day 10 versus Day12) (potential treatment effect).
Time frame: Blood eosinophils measured pre and post allergen (Day 10 versus Day12 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 10 vs Day 12. | 0.1061 10^9 Eosinophils/L | Standard Deviation 0.12225 |
| Placebo | The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 10 vs Day 12. | 0.1846 10^9 Eosinophils/L | Standard Deviation 0.12272 |
Secondary
The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 1 vs Day 10.
Changes in allergen-induced airway and systemic biomarkers (i.e. eosinophils (blood) (Day 1 versus Day 10) (potential treatment effect).
Time frame: Blood eosinophils measured pre allergen (Day 1 versus Day10 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 1 vs Day 10. | 0.0461 10^9 Eosinophils/L | Standard Deviation 0.09546 |
| Placebo | The Effect of Study Treatments on Allergen (HDM)-Induced Changes in Blood Eosinophils, Day 1 vs Day 10. | 0.0211 10^9 Eosinophils/L | Standard Deviation 0.09952 |
Secondary
To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10), Through Measurement of PC20FEV1.
Changes in PC20FEV1(Meth) or PC20FEV1(Hist) Day 1 versus Day 10 (potential treatment effect) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma.
Time frame: PC20FEV1(Meth) or PC20FEV1(Hist) measured pre-allergen (Day 1 versus Day10 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10), Through Measurement of PC20FEV1. | 0.855 mg/mL | Standard Deviation 2.3187 |
| Placebo | To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10), Through Measurement of PC20FEV1. | 1.030 mg/mL | Standard Deviation 2.0795 |
Other Pre-specified
To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 10 Versus Day 12), Through Measurement of Fractionated Nitric Oxide (FeNO).
FeNO is measured from exhaled air by Niox Vero® device (Circassia, Oxford, United Kingdom) according to guidelines in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma.
Time frame: FeNO measured pre and post allergen (Day 10 versus Day12 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 10 Versus Day 12), Through Measurement of Fractionated Nitric Oxide (FeNO). | 44.94 ppb | Standard Deviation 29.952 |
| Placebo | To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 10 Versus Day 12), Through Measurement of Fractionated Nitric Oxide (FeNO). | 67.13 ppb | Standard Deviation 41.906 |
Other Pre-specified
To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10) , Through Measurement of Fractionated Nitric Oxide (FeNO).
FeNO is measured from exhaled air by Niox Vero® device (Circassia, Oxford, United Kingdom) according to guidelines in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma.
Time frame: FeNO measured pre allergen (Day 1 versus Day10 in period 1 and period 2) in Mild Eosinophilic House Dust Mite (HDM)-Allergic Asthma
Population: Of the total 22 subjects who completed both periods 3 were not included in the final analysis: 1 in the FP-025-placebo sequence due to poor PFT variability throughout trial periods, 2 in the placebo-FP-025 sequence due to high deviation in the PC20FEV1(Meth) test results between period 1 and period 2. In addition, carry-over effect was detected in the period 2(placebo) data for FP-025-placebo sequence. Thus the final subjects analyzed include 19 FP-025 treated and 8 placebo treated patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-025 | To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10) , Through Measurement of Fractionated Nitric Oxide (FeNO). | -8.12 ppb | Standard Deviation 19.258 |
| Placebo | To Determine the Treatment Effect (FP-025 Versus Placebo) on Baseline Parameters (i.e. Day 1 Versus Day 10) , Through Measurement of Fractionated Nitric Oxide (FeNO). | -1.96 ppb | Standard Deviation 7.712 |