| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| JNJ-40929837 is being developed for the treatment of asthma. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the allergen-induced late asthmatic response (LAR), as measured by maximal percent fall in FEV1, in subjects with stable mild atopic asthma after treatment with JNJ 40929837 compared to placebo. |
|
| E.2.2 | Secondary objectives of the trial |
•To compare the effects of JNJ 40929837 and placebo on allergen induced EAR, as measured by maximal percent fall in FEV1
•To compare the effects of JNJ 40929837 and placebo on allergen induced EAR and LAR, as measured by area under the FEV1/time curves
•To evaluate the safety of JNJ 40929837
•To characterize the pharmacokinetic and pharmacodynamic relationship of JNJ 40929837 and sputum LTB4 (Sputum Substudy)
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| A substudy will be performed with at least 12 subjects who can produce an adequate sputum sample at screening. These subjects will undergo sputum induction for analysis of cell counts, RNA and other biomarkers in the sputum. All study procedures for subjects who are or are not in the sputum substudy will be identical, with the exception that sputum induction during treatment periods will only be done for subjects in the substudy. |
|
| E.3 | Principal inclusion criteria |
Potential subjects must satisfy all of the following criteria to be enrolled in the study:
1.Are between 18 and 55 years of age, inclusive
2.With the exception of atopic disease (such as allergic rhinitis and atopic dermatitis), are healthy on the basis of:
a.physical examination, medical history, vital signs, and 12 lead ECG performed at screening
b.clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator
3.Have mild atopic asthma requiring no other treatment besides occasional short acting beta2 agonists (see exclusion criterion 76.d.)
4.Have an FEV1 at Screening Visit 1 at least 75% of the predicted value
5.Have a history of asthma symptoms during exposure to indoor or outdoor allergens and a positive skin prick test done at the study site to Der p1, mixed grass pollen, or cat dander
6.Have allergen induced early asthmatic response (EAR) of at least a 20% reduction in FEV1 and late asthmatic response (LAR) of at least a 15% reduction in FEV1 during bronchial allergen challenge (BAC) performed at screening
7.Women must Be one of the following prior to entry:
a)postmenopausal (not experiencing a menstrual period for a minimum of two years), confirmed by a documented serum follicle stimulating hormone (FSH) level >40 IU/L
b)surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), supported with clinical documentation
c)abstinent (at the discretion of the investigator/per local regulations)
d)be practicing a highly effective method of birth control, if sexually active, including hormonal prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel), or male partner sterilization,
consistent with local regulations regarding use of birth control methods for subjects participating in clinical trials, for the duration of their participation in the study. Note: hormonal contraceptives must have been used consistently for 3 months prior to screening
8.Male subjects must consent to utilize a medically acceptable method of contraception throughout the study and not donate sperm during the study. Medically acceptable methods of contraception that may be used by the subject and/or the partner include abstinence, diaphragm with vaginal spermicide, IUD, condom and partner using vaginal spermicide, surgical sterilization (6 months post surgery), post-menopausal partner (not experiencing a menstrual period for a
minimum of two years) and hormonal contraceptives (which must be used consistently for 3 months prior to screening) such as oral contraceptives, hormonal patches, progestin implants or injections, and etonogestrel/ ethinyl estradiol vaginal rings (NuvaRing).
9.Female subjects must have a negative serum pregnancy test at screening
10.Have a negative alcohol test at screening
11.Be willing/able to adhere to the prohibitions and restrictions specified in this protocol
12.Have a negative urine drug test at screening
13.Have a negative urine cotinine test at screening
14.Have a negative QuantiFERON-TB Gold test at screening or a documented negative TB test within the past 6 months, at the discretion of the investigator.
15.Have signed an informed consent document approved by the investigator’s Research Ethics Board indicating that they understand the purpose of and procedures required for the study and are willing to participate in the
study
16.To participate in the optional pharmacogenomic component of this study, subjects must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit). Refusal to give consent for this
component does not exclude a subject from participation in the clinical study
Sputum Substudy – Additional Inclusion Criterion
1.Upon hypertonic saline induction, be able to produce sputum of acceptable quality based on the requirements of the sputum central reading laboratory
|
|
| E.4 | Principal exclusion criteria |
Potential subjects who meet any of the following criteria will be excluded from participating in the study:
1.Have a significant medical condition aside from asthma and other atopic diseases (such as allergic rhinitis and atopic dermatitis)
2.Have a recent myocardial infarction (<3 months), recent cerebral vascular accident (<3 months) or known arterial aneurysm
3.Have had a worsening of asthma or a respiratory tract infection within 6 weeks prior to screening
4.Use of any prescription (except short-acting β agonists [SABAs] as described below and hormonal contraceptives) within 14 days of screening procedures unless approved by the medical monitor.
5.Use of nonprescription drugs (including vitamins, minerals and herbal supplements including herbal medications, "energy" drinks, or products such as Hypericum perforatum [St John's Wort], Ephedra, Ginkgo, Ginseng) within 14 days of screening procedures. The use of paracetamol is allowed until 3 days before the first
dose of study drug.
6.Prophylactic use of short-acting β agonists (SABAs) to prevent exercise induced bronchospasm
7.Use of SABAs more than 3 times per week in the 4 weeks prior to screening
8.Have used disallowed therapies:
a.Inhaled corticosteroids (ICS) or systemic corticosteroids within 2 months prior to screening
b.Anti leukotriene (LT) agents within 2 weeks prior to screening
c.Theophylline-containing products within 2 weeks prior to screening
d.Long acting β agonists within 48 hours prior to screening
e.Anti-IgE within 6 months of screening
f.Allergen immunotherapy within 6 months of screening
9.Have clinically significant abnormal physical examination, vital signs or 12 lead ECG at screening as deemed appropriate by the investigator
10.Have confirmed QTcF interval duration of >450 msec (men) or >460 msec (women) at screening, a history of risk factors for torsades de pointe (eg, heart failure, hypokalemia, family history of Long QT Syndrome), or are currently using medications that prolong the QT/QTc interval or that inhibit P glycoprotein
11.Have used tobacco products of any kind currently or within the 6 months prior to screening or have a smoking history >10 pack years
12.Consumption of poppy seed containing foods within 3 days of screeningstudy visit 1
13.Have a positive anti HCV or evidence of HBV infection (positive HBsAg and/or HBcAb test) at screening
14.Have known allergies, hypersensitivity, or intolerance to JNJ 40929837, montelukast, or their excipients (refer to Section 14.1, Physical Description of Study Drug[s])
15.Have received an investigational drug (including vaccines) or used an investigational medical device within 30 days before screening or are currently enrolled in an investigational study
16.Have donated blood or blood products or had substantial loss of blood (more than 500 mL) within 3 months before the first administration of study drug or intention to donate blood or blood products during the study or within 90 days after the completion of the study
17.Are pregnant, nursing, or planning pregnancy within one year after screening
18.Have any condition that, in the opinion of the investigator, would compromise the well being of the subject or the study or prevent the subject from meeting or performing study requirements, including inability to understand the procedures and the implications of challenge testing
19.Are known to have a current substance abuse (drug, alcohol, or nicotine) problem
20.Have difficulty swallowing the capsule provided in the swallow test
21.Are employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator
22.Are not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
23.Are vulnerable subjects (eg, persons kept in detention) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| •Maximal percent fall in FEV1 between 3 to 10 hours post allergen challenge from pre allergen challenge |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | Yes |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 2 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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