To Investigate the Efficacy and Safety of OPC-6535 in Chronic Obstructive Pulmonary Disease (COPD) Patients
Sponsor
Otsuka Pharmaceutical Co., Ltd. (Industry)
Overall Status
Completed
CT.gov ID
NCT00917150
Collaborator
(none)
771
9
4
61
85.7
1.4
Study Details
Study Description
Brief Summary
To investigate the efficacy and safety of OPC-6535 in COPD patients, using the measurement of trough FEV1 over time as the primary endpoint.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
771 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Multinational, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-arm, Dose-comparison Trial of OPC-6535 in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study Start Date
:
Mar 1, 2009
Actual Primary Completion Date
:
Apr 1, 2014
Actual Study Completion Date
:
Apr 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: OPC-6535 12.5mg
|
Drug: tetomilast (OPC-6535)
oral administration of 12.5mg OPC-6535, once daily for 24months
|
| Experimental: OPC-6535 25mg
|
Drug: tetomilast (OPC-6535)
oral administration of 25mg OPC-6535, once daily for 24months
|
| Experimental: OPC-6535 50mg
|
Drug: tetomilast (OPC-6535)
oral administration of 50 mg OPC-6535, once daily for 24months
|
| Placebo Comparator: placebo
|
Drug: placebo
oral administration of placebo, once daily for 24months
|
Outcome Measures
Primary Outcome Measures
- Trough Forced Expiratory Volume in 1 Second (FEV1) Change From Baseline to 24 Months [Baseline, 24 months]
Measurement over time (from baseline over the 24-month treatment period) and change from baseline to end of the treatment period.
Secondary Outcome Measures
- Change From Baseline at 24 Months in Total Symptom Diary Score [Baseline, 24 months]
Subjects were required to keep a symptom diary throughout the entire trial period from the start of investigational medicinal product (IMP) administration in the washout period until the end of the treatment period. Assessment items included scores for shortness of breath, cough, and sputum, IMP compliance, use of salbutamol and respiratory symptom medications, and smoking status. Subjects recorded a score of between 0 and 3, with 0 indicating no symptoms and 3 indicating a high level of symptoms, for each domain.
- Change From Baseline at 24 Months in St. George's Respiratory Questionnaire (SGRQ) Total Score [Baseline, 24 months]
The SGRQ is a self-administered questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being in three domains: symptoms, activity, and impact on daily life. The SGRQ was completed by each subject prior to IMP administration at baseline and at Month 6, Month 12, Month 18, and Month 24 (end of treatment). A weighted score based on population norms for each dimension and total was evaluated. Scores were expressed as a percentage of overall impairment where 100 represented worst possible health status and 0 indicated best possible health status. Scores were calculated when less than 24% of the item scores were missing, otherwise the scores were set to missing. Where there were multiple answers for a question, the worst case was used.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age 40 to 75 years, inclusive, at the time informed consent is obtained
-
Ability to provide own written informed consent
-
Agree to use an appropriate method of contraception until 3 months after the last dose of the investigational medicinal product (IMP)
-
A rating of 1 or higher on the Goddard scale in assessment of emphysema severity by chest CT scan at screening
-
Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) of less than 70% at screening
-
Cigarette smoking history of at least 20 pack years at screening
Exclusion Criteria:
-
Subjects with obstructive disorders due to bronchial asthma
-
Subjects receiving long-term oxygen therapy
-
Subjects with active tuberculosis or obvious bronchiectasis
-
Complication of malignant tumor
-
Uncontrolled cardiovascular, endocrine, blood, or nervous system disorders
-
Uncontrolled condition with COPD exacerbation of level 2 or 3 within 8 weeks prior to the start of washout period (within 12 weeks prior to start of treatment period)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Central China Area | China | |||
| 2 | East China Area | China | |||
| 3 | North China Area | China | |||
| 4 | Northeast China Area | China | |||
| 5 | Northwest China Area | China | |||
| 6 | South China Area | China | |||
| 7 | Southwest China Area | China | |||
| 8 | Kansai Region, Et Al. | Japan | |||
| 9 | Seoul, Et Al. | Korea, Republic of |
Sponsors and Collaborators
- Otsuka Pharmaceutical Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT00917150
Other Study ID Numbers:
- 197-08-801
- JapicCTI-090770
First Posted:
Jun 10, 2009
Last Update Posted:
Apr 30, 2021
Last Verified:
Apr 1, 2021
Keywords provided by Otsuka Pharmaceutical Co., Ltd.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Oral administration of 12.5mg OPC-6535 once daily for 24 months | Oral administration of 25mg OPC-6535 once daily for 24 months | Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week) | Oral administration of placebo once daily for 24 months |
| Period Title: Overall Study | ||||
| STARTED | 192 | 198 | 191 | 190 |
| COMPLETED | 155 | 161 | 149 | 156 |
| NOT COMPLETED | 37 | 37 | 42 | 34 |
Baseline Characteristics
| Arm/Group Title | OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Oral administration of 12.5mg OPC-6535 once daily for 24 months | Oral administration of 25mg OPC-6535 once daily for 24 months | Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week) | Oral administration of placebo once daily for 24 months | Total of all reporting groups |
| Overall Participants | 192 | 198 | 191 | 190 | 771 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
62.2
(7.63)
|
64.0
(7.01)
|
63.2
(7.55)
|
63.4
(7.24)
|
63.2
(7.37)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
14
7.3%
|
7
3.5%
|
18
9.4%
|
15
7.9%
|
54
7%
|
| Male |
178
92.7%
|
191
96.5%
|
173
90.6%
|
175
92.1%
|
717
93%
|
| Region of Enrollment (Count of Participants) | |||||
| South Korea |
32
16.7%
|
37
18.7%
|
35
18.3%
|
32
16.8%
|
136
17.6%
|
| Japan |
12
6.3%
|
13
6.6%
|
10
5.2%
|
10
5.3%
|
45
5.8%
|
| China |
148
77.1%
|
148
74.7%
|
146
76.4%
|
148
77.9%
|
590
76.5%
|
Outcome Measures
| Title | Trough Forced Expiratory Volume in 1 Second (FEV1) Change From Baseline to 24 Months |
|---|---|
| Description | Measurement over time (from baseline over the 24-month treatment period) and change from baseline to end of the treatment period. |
| Time Frame | Baseline, 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population consisted of all subjects randomized to double-blind therapy, regardless of any protocol violation. |
| Arm/Group Title | OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Oral administration of 12.5mg OPC-6535 once daily for 24 months | Oral administration of 25mg OPC-6535 once daily for 24 months | Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week) | Oral administration of placebo once daily for 24 months |
| Measure Participants | 152 | 163 | 152 | 149 |
| Mean (Standard Error) [Liters] |
-0.004
(0.0481)
|
-0.023
(0.0481)
|
-0.018
(0.0473)
|
-0.035
(0.0480)
|
| Title | Change From Baseline at 24 Months in Total Symptom Diary Score |
|---|---|
| Description | Subjects were required to keep a symptom diary throughout the entire trial period from the start of investigational medicinal product (IMP) administration in the washout period until the end of the treatment period. Assessment items included scores for shortness of breath, cough, and sputum, IMP compliance, use of salbutamol and respiratory symptom medications, and smoking status. Subjects recorded a score of between 0 and 3, with 0 indicating no symptoms and 3 indicating a high level of symptoms, for each domain. |
| Time Frame | Baseline, 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population consisted of all subjects randomized to double-blind therapy, regardless of any protocol violation. |
| Arm/Group Title | OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Oral administration of 12.5mg OPC-6535 once daily for 24 months | Oral administration of 25mg OPC-6535 once daily for 24 months | Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week) | Oral administration of placebo once daily for 24 months |
| Measure Participants | 150 | 161 | 152 | 151 |
| Mean (Standard Error) [score on a scale] |
0.063
(0.0606)
|
0.073
(0.0606)
|
0.077
(0.0597)
|
0.101
(0.0606)
|
| Title | Change From Baseline at 24 Months in St. George's Respiratory Questionnaire (SGRQ) Total Score |
|---|---|
| Description | The SGRQ is a self-administered questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being in three domains: symptoms, activity, and impact on daily life. The SGRQ was completed by each subject prior to IMP administration at baseline and at Month 6, Month 12, Month 18, and Month 24 (end of treatment). A weighted score based on population norms for each dimension and total was evaluated. Scores were expressed as a percentage of overall impairment where 100 represented worst possible health status and 0 indicated best possible health status. Scores were calculated when less than 24% of the item scores were missing, otherwise the scores were set to missing. Where there were multiple answers for a question, the worst case was used. |
| Time Frame | Baseline, 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population consisted of all subjects randomized to double-blind therapy, regardless of any protocol violation. |
| Arm/Group Title | OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo |
|---|---|---|---|---|
| Arm/Group Description | Oral administration of 12.5mg OPC-6535 once daily for 24 months | Oral administration of 25mg OPC-6535 once daily for 24 months | Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week) | Oral administration of placebo once daily for 24 months |
| Measure Participants | 151 | 157 | 148 | 151 |
| Mean (Standard Error) [score on a scale] |
-9.6
(3.80)
|
-7.9
(3.80)
|
-7.7
(3.73)
|
-10.4
(3.80)
|
Adverse Events
| Time Frame | Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP. | |||||||
| Arm/Group Title | OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo | ||||
| Arm/Group Description | Oral administration of 12.5mg OPC-6535 once daily for 24 months | Oral administration of 25mg OPC-6535 once daily for 24 months | Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week) | Oral administration of placebo once daily for 24 months | ||||
All Cause Mortality |
||||||||
| OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/192 (0.5%) | 5/196 (2.6%) | 3/191 (1.6%) | 2/190 (1.1%) | ||||
Serious Adverse Events |
||||||||
| OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/192 (24.5%) | 47/196 (24%) | 50/191 (26.2%) | 46/190 (24.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Splenomegaly | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Cardiac disorders | ||||||||
| Cor pulmonale | 1/192 (0.5%) | 2/196 (1%) | 0/191 (0%) | 2/190 (1.1%) | ||||
| Angina pectoris | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 1/190 (0.5%) | ||||
| Coronary artery disease | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Arteriosclerosis coronary artery | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Atrial fibrillation | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Cardiac failure congestive | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Cor pulmonale chronic | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Hypertensive heart disease | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Ischaemic cardiomyopathy | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Prinzmetal angina | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Supraventricular tachycardia | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Congenital, familial and genetic disorders | ||||||||
| Chronic granulomatous disease | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Eye disorders | ||||||||
| Cataract | 0/192 (0%) | 0/196 (0%) | 2/191 (1%) | 2/190 (1.1%) | ||||
| Gastrointestinal disorders | ||||||||
| Inguinal hernia | 0/192 (0%) | 0/196 (0%) | 3/191 (1.6%) | 1/190 (0.5%) | ||||
| Colonic polyp | 2/192 (1%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Gastric polyps | 1/192 (0.5%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Abdominal distension | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Abdominal pain upper | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Constipation | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Duodenal ulcer perforation | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Enterocolitis | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Gastritis | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Gastritis erosive | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Gingival cyst | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Haemorrhoids | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Ileus | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Nausea | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Upper gastrointestinal haemorrhage | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Vomiting | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholelithiasis | 0/192 (0%) | 1/196 (0.5%) | 1/191 (0.5%) | 2/190 (1.1%) | ||||
| Cholecystitis acute | 0/192 (0%) | 0/196 (0%) | 2/191 (1%) | 0/190 (0%) | ||||
| Hepatic cirrhosis | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Bile duct stone | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Cholangitis acute | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Infections and infestations | ||||||||
| Pneumonia | 7/192 (3.6%) | 2/196 (1%) | 2/191 (1%) | 5/190 (2.6%) | ||||
| Upper respiratory tract infection | 1/192 (0.5%) | 1/196 (0.5%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Pulmonary tuberculosis | 1/192 (0.5%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Sinusitis | 0/192 (0%) | 1/196 (0.5%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Appendicitis | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Bronchitis | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Bronchopneumonia | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Cellulitis | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Hepatitis C | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Herpes zoster | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Herpes zoster infection neurological | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Influenza | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Lobar pneumonia | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Lung infection | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Nasopharyngitis | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Pneumonia bacterial | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Pseudomembranous colitis | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Pulmonary tuberculoma | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Septic shock | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Femur fracture | 0/192 (0%) | 2/196 (1%) | 1/191 (0.5%) | 1/190 (0.5%) | ||||
| Femoral neck fracture | 0/192 (0%) | 1/196 (0.5%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Hand fracture | 0/192 (0%) | 0/196 (0%) | 2/191 (1%) | 0/190 (0%) | ||||
| Ankle fracture | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Concussion | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Contusion | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Excoriation | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Head injury | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Humerus fracture | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Joint injury | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Meniscus lesion | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Muscle strain | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Rib fracture | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Traumatic liver injury | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Investigations | ||||||||
| Computerised tomogram thorax abnormal | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Electrocardiogram QT prolonged | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Diabetes mellitus | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Type 2 diabetes mellitus | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Spondylolisthesis | 1/192 (0.5%) | 0/196 (0%) | 1/191 (0.5%) | 1/190 (0.5%) | ||||
| Intervertebral disc protrusion | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Lumbar spinal stenosis | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Chondromalacia | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Muscular weakness | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Osteoporosis | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Rotator cuff syndrome | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Spinal column stenosis | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Lung neoplasm malignant | 1/192 (0.5%) | 2/196 (1%) | 2/191 (1%) | 2/190 (1.1%) | ||||
| Bladder cancer | 0/192 (0%) | 2/196 (1%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Astrocytoma malignant | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Bone neoplasm | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Brain cancer metastatic | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Breast cancer | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Chronic myelomonocytic leukaemia | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Gastric cancer | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Head and neck cancer | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Hepatic cancer metastatic | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Large cell lung cancer stage IV | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Large intestine carcinoma | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Lung neoplasm | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Neuroendocrine tumour | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Non-small cell lung cancer | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Prostate cancer | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Renal cell carcinoma | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Salivary gland neoplasm | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Nervous system disorders | ||||||||
| Hypoxic encephalopathy | 1/192 (0.5%) | 1/196 (0.5%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Cerebral haemorrhage | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Cerebral infarction | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Cerebrovascular accident | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Epilepsy | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Hypoaesthesia | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Intraventricular haemorrhage | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Neuritis | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Polyneuropathy | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Spinal meningeal cyst | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Subarachnoid haemorrhage | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Vertebrobasilar insufficiency | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Psychiatric disorders | ||||||||
| Depression | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Dyssomnia | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Dysuria | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Urinary retention | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 1/192 (0.5%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
| Varicocele | 0/192 (0%) | 0/196 (0%) | 0/191 (0%) | 1/190 (0.5%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic obstructive pulmonary disorder | 22/192 (11.5%) | 24/196 (12.2%) | 22/191 (11.5%) | 24/190 (12.6%) | ||||
| Pneumothorax | 1/192 (0.5%) | 4/196 (2%) | 2/191 (1%) | 0/190 (0%) | ||||
| Respiratory failure | 2/192 (1%) | 3/196 (1.5%) | 1/191 (0.5%) | 1/190 (0.5%) | ||||
| Hiccups | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Atelectasis | 1/192 (0.5%) | 0/196 (0%) | 0/191 (0%) | 0/190 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Dermal cyst | 0/192 (0%) | 0/196 (0%) | 1/191 (0.5%) | 0/190 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/192 (0%) | 1/196 (0.5%) | 0/191 (0%) | 0/190 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| OPC-6535 12.5 mg | OPC-6535 25 mg | OPC-6535 50 mg | Placebo | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 108/192 (56.3%) | 116/196 (59.2%) | 102/191 (53.4%) | 105/190 (55.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Thrombocytopenia | 8/192 (4.2%) | 4/196 (2%) | 2/191 (1%) | 4/190 (2.1%) | ||||
| Cardiac disorders | ||||||||
| Angina pectoris | 1/192 (0.5%) | 2/196 (1%) | 4/191 (2.1%) | 1/190 (0.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 9/192 (4.7%) | 10/196 (5.1%) | 18/191 (9.4%) | 8/190 (4.2%) | ||||
| Abdominal pain upper | 8/192 (4.2%) | 11/196 (5.6%) | 10/191 (5.2%) | 3/190 (1.6%) | ||||
| Gastritis | 3/192 (1.6%) | 7/196 (3.6%) | 9/191 (4.7%) | 5/190 (2.6%) | ||||
| Abdominal distension | 4/192 (2.1%) | 4/196 (2%) | 6/191 (3.1%) | 0/190 (0%) | ||||
| Abdominal discomfort | 2/192 (1%) | 3/196 (1.5%) | 8/191 (4.2%) | 1/190 (0.5%) | ||||
| Toothache | 4/192 (2.1%) | 4/196 (2%) | 2/191 (1%) | 3/190 (1.6%) | ||||
| Nausea | 3/192 (1.6%) | 2/196 (1%) | 5/191 (2.6%) | 1/190 (0.5%) | ||||
| Gastrooesophageal reflux disease | 5/192 (2.6%) | 3/196 (1.5%) | 2/191 (1%) | 1/190 (0.5%) | ||||
| Abdominal pain | 0/192 (0%) | 0/196 (0%) | 6/191 (3.1%) | 1/190 (0.5%) | ||||
| Dyspepsia | 2/192 (1%) | 4/196 (2%) | 1/191 (0.5%) | 1/190 (0.5%) | ||||
| General disorders | ||||||||
| Pyrexia | 4/192 (2.1%) | 3/196 (1.5%) | 5/191 (2.6%) | 1/190 (0.5%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 33/192 (17.2%) | 21/196 (10.7%) | 19/191 (9.9%) | 22/190 (11.6%) | ||||
| Pneumonia | 4/192 (2.1%) | 1/196 (0.5%) | 2/191 (1%) | 1/190 (0.5%) | ||||
| Investigations | ||||||||
| Blood creatine phosphokinase increased | 5/192 (2.6%) | 2/196 (1%) | 5/191 (2.6%) | 4/190 (2.1%) | ||||
| Protein urine present | 1/192 (0.5%) | 4/196 (2%) | 1/191 (0.5%) | 2/190 (1.1%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Anorexia | 4/192 (2.1%) | 2/196 (1%) | 10/191 (5.2%) | 4/190 (2.1%) | ||||
| Hyperlipidaemia | 1/192 (0.5%) | 4/196 (2%) | 0/191 (0%) | 2/190 (1.1%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Myalgia | 2/192 (1%) | 7/196 (3.6%) | 3/191 (1.6%) | 3/190 (1.6%) | ||||
| Nervous system disorders | ||||||||
| Headache | 7/192 (3.6%) | 8/196 (4.1%) | 3/191 (1.6%) | 3/190 (1.6%) | ||||
| Dizziness | 2/192 (1%) | 7/196 (3.6%) | 3/191 (1.6%) | 1/190 (0.5%) | ||||
| Renal and urinary disorders | ||||||||
| Proteinuria | 5/192 (2.6%) | 2/196 (1%) | 2/191 (1%) | 3/190 (1.6%) | ||||
| Reproductive system and breast disorders | ||||||||
| Benign prostatic hyperplasia | 6/192 (3.1%) | 4/196 (2%) | 3/191 (1.6%) | 4/190 (2.1%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic obstructive pulmonary disease | 58/192 (30.2%) | 67/196 (34.2%) | 52/191 (27.2%) | 57/190 (30%) | ||||
| Productive cough | 4/192 (2.1%) | 8/196 (4.1%) | 5/191 (2.6%) | 4/190 (2.1%) | ||||
| Oropharyngeal pain | 7/192 (3.6%) | 6/196 (3.1%) | 2/191 (1%) | 3/190 (1.6%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 4/192 (2.1%) | 8/196 (4.1%) | 5/191 (2.6%) | 4/190 (2.1%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Director of Clinical Trials |
|---|---|
| Organization | Otsuka Pharmaceutical Co., LTD. |
| Phone | +81-3-6361-7366 |
| CL_OPCJ_RDA_Team@otsuka.jp |
Responsible Party:
Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT00917150
Other Study ID Numbers:
- 197-08-801
- JapicCTI-090770
First Posted:
Jun 10, 2009
Last Update Posted:
Apr 30, 2021
Last Verified:
Apr 1, 2021