A double-blind, placebo-controlled efficacy (as assessed by post-bronchodilator FEV1) and safety study of 5 mg RO3300074 once-daily for 2 years in subjects with smoking-related, moderate-to-severe COPD with emphysema receiving concurrent optimal COPD drug therapy.
- Conditions
- symptomatic smoking-related emphysema in ex-smokersMedDRA version: 8.1Level: LLTClassification code 10014561Term: Emphysema
- Registration Number
- EUCTR2006-002525-23-HU
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 480
Inclusion criteria at screening:
1. Ex-smokers with 10 or more pack-year smoking history (subjects must have stopped smoking for ? 12 months prior to enrollment)
2. Subjects of > 44 years of age. Women must be more than 2 years post-menopausal or have had a hysterectomy or bilateral oophorectomy.
3. Men with partners of child-bearing potential must agree to use barrier contraception during the study and for 30 days after discontinuation of treatment.
4. Subjects with moderate to severe COPD defined as follows:
Post-bronchodilator FEV1 / FVC < 70%
Post-bronchodilator FEV1 value at screening visit greater than or equal to 35% and less than or equal to 70 % of the predicted normal value will be met at time of randomization (Visit 2), Dl,co (Tl,co) < 70% of the predicted normal value, MMRC symptom score > 1 (see appendix7).
5. Subjects must be able to participate in the study, willing to give written informed consent, and comply with the study restrictions.
6. Subjects must be able to swallow gelatine capsules within 30 minutes after eating breakfast on a daily basis.
7. Subjects must agree to be switched to optimal COPD drug therapy at screening. Optimal COPD drug therapy consists of short-acting bronchodilators as needed and Tiotropium (DPI) and either Salmeterol/Fluticasone (DPI) or Formoterol/Budesonide (DPI) at the highest doses approved by regulatory authorities.
Note: Subjects who must be switched to optimal COPD drug therapy must be treated for 6 weeks before attending the randomization visit. The other subjects may be randomized earlier.
8. Subjects have been off oral steroids > 28 days prior to screening visit (eg. Prednisone, Prednisolone).
Inclusion criteria at randomisation:
1. Emphysema confirmed by qualitative low-dose, spiral CT performed and officially interpreted within 28 days of expected randomization.
2. Post-bronchodilator FEV1 / FVC < 70%.
3. Post-bronchodilator FEV1 value at randomization visit greater than or equal to 35% and less than or equal to 70% of the predicted normal value for gender, age, and height.
4. Dl,co (Tl,co) < 70% of the predicted normal value
5. Since screening visit no exacerbation of pulmonary symptoms, requiring hospitalization or treatment with oral steroids, or antibiotics.
6. Subjects have been off oral steroids since screening visit (eg. Prednisone, Prednisolone).
7. Subjects must be able to perform the 6-minute walk test.
8. Subjects must not have any changes to medication or treatments for COPD after screening visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Within 12 months prior to screening: more than 2 exacerbations of pulmonary symptoms requiring out patient treatment with oral steroids or antibiotics, or more than 1 exacerbation if the latter required hospitalization.
2. Observation of a solitary nodule (> 8 mm) in the lung (see appendix 9 in the protocol for guidelines of lung nodules).
3. Subjects with giant bullous disease of > 1/3 of a hemithorax.
4. Any predominant diagnosis of bronchiectasis, tuberculosis, interstitial fibrosis, asbestosis, cystic fibrosis.
5. Subjects on lung transplant waiting list.
6. Subjects who have undergone lung volume reduction surgery.
7. Significant other medical conditions, which in the opinion of the investigator, will interfere with the subject’s ability to perform the study tests.
8. Currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations (see protocol section 4.4).
9. Exposure to synthetic oral retinoids in the past 12 months.
10. Hypertriglyceridemia ? 300 mg/dl (3.4 mmol/dl) with or without therapy.
11. Unexplained weight loss of ? 10% of total body weight over the last 6 months or body mass index < 19 kg/m2.
12. History of allergy or sensitivity to retinoids.
13. Concurrent enrollment or participation in any other therapeutic clinical trial within the last 30 days.
14. Medical history or active conditions likely to compromise the safety of the subject, or the absorption, metabolism, or excretion of the study medication. This includes, but is not limited to: Psychiatric disorders, skin disorders, cancer, convulsive disorder, bleeding disorders, current lung cancer or history of lung cancer, renal failure, cirrhosis or chronic liver disease, pancreatic diseases, leukopenia, thrombocytopenia, active infection, myocardial infarction, angina, or coronary artery disease within the last 6 months.
15. History of substance abuse excepting nicotine (i.e. drug, alcohol).
16. Elevated ALT>2.5x the upper normal limit.
17. Elevated Amylase >1.5 above the upper normal limit.
18. Elevated Lipase >1.5 above the upper normal limit.
19. Concomitant medications which are inhibitors or inducers of CYP 450 3A4 activity as defined in the protocol (see section 4.4). (Assuming subjects cannot or will not elect to stop these medications)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method