Clinical trial NCT00698828: SUN11031 in Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Phase 2b, Multicenter, Randomized, Double-Blind, Parallel, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SUN11031 for Injection Administered Subcutaneously Twice Daily for 12 Weeks to Subjects Having Cachexia Associated With Chronic Obstructive Pulmonary Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cachexia
Keywords: Cachexia, COPD, Chronic Obstructive Pulmonary Disease
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2008-06-17
Enrollment: 227
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate SUN11031 for subcutaneous injection compared to placebo in subjects with cachexia associated with Chronic Obstructive Pulmonary Disease (COPD) to determine the effect on physical performance and body composition.


Eligibility criteria: Inclusion Criteria:

Each participant had to meet the following criteria to be enrolled in the study:

1. Male or non-pregnant female participants 50 years or older with a clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) for greater than or equal to 12 months
2. Walked a distance of greater than or equal to 100 but less than or equal to 450 meters during the 6-Minute Walk Test (MWT) performed at screening.
3. Chest x-ray within the past year that was compatible with COPD
4. Documented involuntary nonedematous weight loss of greater than 5% of participant's usual body weight over the past 12 months or BMI less than or equal to 21 kg/m\^2 for males or Body Mass Index (BMI) less than or equal to 20 kg/m\^2 for females
5. Female participants who were clinically sterile (eg, either postmenopausal or had undergone a tubal ligation or hysterectomy) or were practicing a medically acceptable method of birth control (eg, oral, transdermal, implantable, or injectable contraceptive medications; double-barrier method or intrauterine device)

Exclusion Criteria:

Participants who met any of the following criteria were excluded from the study:

1. BMI greater than 26 kg/m\^2
2. Used, over a total of 7 or more days, parenteral corticosteroids at a dose equivalent to prednisone at greater than or equal to 5 mg/day or oral corticosteroids at a dose equivalent to prednisone at greater than 10 mg/day within the 2 months before screening; however, participants were allowed to participate if on stable doses equivalent to prednisone at less than or equal to 10 mg/day for at least 2 months before screening, and were planning to remain on the same stable dose throughout the study
3. Were planning to start a pulmonary rehabilitation program during the study (participant may have been enrolled in the study if he or she was currently on a stable maintenance program)
4. Weight loss that was considered to be, in the opinion of the investigator, the result of food deprivation
5. Unintended weight loss that may have been due to disease other than COPD
6. Unable or unwilling to be trained to self-administer the study drug by subcutaneous injection bid, and for whom arrangements could not be made for a third party to reliably administer the injections
7. Severe anemia (hemoglobin less than or equal to 8 g/dL)
8. COPD exacerbation defined as a Type 1 or 2 exacerbation according to the Winnipeg criteria, acute infection, or prolonged fever within 4 weeks before screening
9. Undergoing treatment or evaluation for cancer, or had a history of treatment for cancer within the past 3 years, exception being nonmelanoma skin cancer (basal cell or squamous cell carcinoma of the skin) and carcinoma in situ of the cervix
10. Type I or type II diabetes mellitus or a fasting serum glucose of greater than or equal to 115 mg/dL (6.4 mmol/L) (fasting was overnight)
11. Serious disease or conditions that would have interfered with the participant's ability to complete the functional measures included in this protocol; or any illness that, in the opinion of the investigator, might have interfered with the results of the study or the participant's ability to participate
12. Pulmonary embolism, deep venous thrombosis, or clinically significant primary pulmonary hypertension within the past 6 months
13. Significant ischemic heart disease or chronic heart failure (New York Heart Association Class IV cardiac disease)
14. Uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 110 mm Hg)
15. A history of symptomatic orthostatic hypotension or syncope; or orthostatic hypotension at screening or baseline (Days -6 to -3) (orthostatic hypotension was defined as a decrease in systolic blood pressure by greater than or equal to 20 mm Hg measured after 2 minutes in a standing position compared with the systolic blood pressure measured after 10 minutes in a supine position)
16. Evidence of ascites, pleural effusion, or lower extremity edema
17. Severe vitamin D deficiency (25-hydroxyvitamin D less than 10 ng/mL)
18. Known mechanical obstruction of the alimentary tract and/or malabsorption
19. Dental or swallowing problems that may have had a negative effect on food intake
20. Serum creatinine greater than 2.5 mg/dL; or alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transferase greater than 3 times the upper limit of normal, or bilirubin greater than 2.5 mg/dL
21. A diagnosis of human immunodeficiency virus infection or AIDS
22. Used any prescription drugs and non-prescription drugs/herbs that cause weight loss or affect appetite and absorption or that may cause nausea; or used appetite-promoting or anabolic medications within 15 days before screening
23. A history of alcohol or drug abuse that, in the opinion of the investigator, would have interfered with the participant's ability to comply with the dosing schedule and protocol-specified requirements
24. Hypersensitive to any component of SUN11031, or participated at any time in any study in which SUN11031 was administered
25. Received an investigational drug or product, or participated in a drug study within 30 days before screening
26. Non-ambulatory or unwilling to cooperate fully with the investigator or a designee, or unwilling or unable to comply with study requirements, such as all assessments required by the protocol, including completion of measures for functional capacity and pulmonary function, or frequent blood sampling and meal instructions; or unable or unwilling to attend all study visits

Primary outcomes:
measure: Mean Change From Baseline to Day 85 in the Distance Walked During the 6 Minute Walk Test (MWT) Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD)
timeFrame: Baseline up to Day 85 post dose.
Secondary outcomes:
measure: Mean Change From Baseline to Days 29, 57, and 85 in the Distance Walked During the 6 Minute Walk Test (MWT) Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD)
timeFrame: Baseline up to Day 29, Day 57, and Day 85 post dose.
measure: Mean Change From Baseline to Days 29, 57, and 85 in the Distance Walked During the 6 Minute Walk Test (MWT) By Sub-groups Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD)
timeFrame: Baseline up to Day 29, Day 57, and Day 85 post dose.
measure: Number of Participants With Improvement in Distance Walked During the 6 Minute Walk Test (MWT) By Sub-groups Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease
timeFrame: Baseline up to Day 85 post dose.
measure: Mean Change in Body Weight From Baseline Through Day 99 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease
timeFrame: Baseline up to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85, and Day 99 post dose.
measure: Mean Change in Lean Body Mass From Baseline Through Days 29, 85 and 99 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease
timeFrame: Baseline up to Day 29, Day 85, and Day 99 post dose.
measure: Absolute Concentrations of SUN11031 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease
timeFrame: Day 1 and Day 85 pre-dose; Day 1 at 1 hour and 4 hours; Day 29 at 0.08 hours and 1.5 hours; Day 57 at 0.08 hours and 6 hours; Day 85 at 0.5 hours and 3 hours postdose.
measure: Absolute Concentrations of SUN11031 Metabolites Desacyl-ghrelin Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease
timeFrame: Day 1 and Day 85 pre-dose; Day 1 at 1 hour and 4 hours; Day 29 at 0.08 hours and 1.5 hours; Day 57 at 0.08 hours and 6 hours; Day 85 at 0.5 hours and 3 hours postdose.
measure: Treatment Emergent Adverse Events Reported in ≥ 2% of Participants Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease
timeFrame: Baseline up to Day 113 post dose, up to a total of 134 days.
Other outcomes:
Locations:
city: Waterbury
country: United States
facility: Waterbury Pulmonary Associates
state: Connecticut
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Largo
country: United States
facility: Innovative Research of West Florida
state: Florida
city: Hagerstown
country: United States
facility: The Center for Clinical Research, Washington County Hospital
state: Maryland
city: Missoula
country: United States
facility: Montana Medical Research, Inc.
state: Montana
city: Papillion
country: United States
facility: The Asthma & Allergy Center
state: Nebraska
city: Cortland
country: United States
facility: Health Science Research Center - Asthma & Allergy Associates
state: New York
city: Cincinnati
country: United States
facility: New Horizons Clinical Research
state: Ohio
city: Medford
country: United States
facility: Clinical Research Institute of Southern Oregon
state: Oregon
city: Spartanburg
country: United States
facility: Spartanburg Medical Research
state: South Carolina
city: Tacoma
country: United States
facility: Pulmonary Consultants
state: Washington
city: Florencío Varela
country: Argentina
facility: Centro de Investigaciones Médicas
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Centro Respiratorio Quilmes
state: Buenos Aires
city: Cipolletti
country: Argentina
facility: Instituto de Investigaciones Clínicas Cipolletti
state: Río Negro
city: Rosario
country: Argentina
facility: Clinica del Tórax
state: Santa Fe
city: Rosario
country: Argentina
facility: Instituto Cardiovascular de Rosario
state: Santa Fe
city: San Miguel de Tucumán
country: Argentina
facility: CEMIT
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Centro de Investigación Médica Lanús
city: Capital Federal
country: Argentina
facility: FAICEP
city: Capital Federal
country: Argentina
facility: Instituto Médico de Asistencia e Investigación
city: Capital Federal
country: Argentina
facility: Centro Médico Dra. De Salvo
city: Capital Federal
country: Argentina
facility: Centro Médico Belgrano
city: Capital Federal
country: Argentina
facility: Centro Ceri
city: Capital Federal
country: Argentina
facility: Centro de Estudios Neumonologicos
city: Mendoza
country: Argentina
facility: Fuesmen
city: Mendoza
country: Argentina
facility: Instituto de Enfermedades Respiratorias
city: Paraná
country: Argentina
facility: Centro de Medicina Respiratoria
city: Tucuman
country: Argentina
facility: Instituto de Patologia Respiratoria
city: Santiago
country: Chile
facility: Hospital Barros Luco Trudeau
city: Santiago
country: Chile
facility: Hospital San Jose
city: Santiago
country: Chile
facility: Integramedica La Florida
city: Guatemala
country: Guatemala
facility: Instituto Pneos
city: Guatemala
country: Guatemala
facility: Edificio Centro Medico II
city: Guatemala
country: Guatemala
facility: Private Clinic
city: Quetzaltenango
country: Guatemala
facility: Edificio Medico San Lucas
city: San Pedro Sula
country: Honduras
facility: Centro de Neumologia y Alergia
city: Tegucigalpa
country: Honduras
facility: Instituto Nacional Cardiopulmonar
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca
state: Cluj
city: Timişoara
country: Romania
facility: Spitalul Clinic de Boli Infectioase si Pneumoftiziologoe "Dr. Victor Babes"
state: Timiş
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca
city: Constanţa
country: Romania
facility: Spitalul Clinic de Pneumoftiziologie Constanta, Cartier Palazul Mare
city: Sibiu
country: Romania
facility: Spitalul Clinic Judetean Sibiu, Clinica Medicala
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: