SUN11031 in Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD)

Cachexia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00698828
• Other study ID #: ASBI 307
• Status: Completed
• Phase: Phase 2
• Start date: May 15, 2008
• Est. completion date: October 8, 2009

Study information

• Verified date: January 2021
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 227
• Est. completion date: October 8, 2009
• Est. primary completion date: October 8, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cachexia
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Placebo comparator
Twice daily subcutaneous injections of placebo for 12 weeks.
• SUN11031 20 µg/kg
Twice daily subcutaneous injections of SUN11031 20 µg/kg for 12 weeks.
• SUN11031 40 µg/kg
Twice daily subcutaneous injections of SUN11031 40 µg/kg for 12 weeks.

Locations

Country	Name	City	State
Argentina	Centro de Investigación Médica Lanús	Buenos Aires
Argentina	Centro Ceri	Capital Federal
Argentina	Centro de Estudios Neumonologicos	Capital Federal
Argentina	Centro Médico Belgrano	Capital Federal
Argentina	Centro Médico Dra. De Salvo	Capital Federal
Argentina	FAICEP	Capital Federal
Argentina	Instituto Médico de Asistencia e Investigación	Capital Federal
Argentina	Instituto de Investigaciones Clínicas Cipolletti	Cipolletti	Río Negro
Argentina	Centro de Investigaciones Médicas	Florencío Varela	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas Mar del Plata	Mar del Plata	Buenos Aires
Argentina	Fuesmen	Mendoza
Argentina	Instituto de Enfermedades Respiratorias	Mendoza
Argentina	Centro de Medicina Respiratoria	Paraná
Argentina	Centro Respiratorio Quilmes	Quilmes	Buenos Aires
Argentina	Clinica del Tórax	Rosario	Santa Fe
Argentina	Instituto Cardiovascular de Rosario	Rosario	Santa Fe
Argentina	CEMIT	San Miguel de Tucumán	Tucumán
Argentina	Instituto de Patologia Respiratoria	Tucuman
Chile	Hospital Barros Luco Trudeau	Santiago
Chile	Hospital San Jose	Santiago
Chile	Integramedica La Florida	Santiago
Guatemala	Edificio Centro Medico II	Guatemala
Guatemala	Instituto Pneos	Guatemala
Guatemala	Private Clinic	Guatemala
Guatemala	Edificio Medico San Lucas	Quetzaltenango
Honduras	Centro de Neumologia y Alergia	San Pedro Sula
Honduras	Instituto Nacional Cardiopulmonar	Tegucigalpa
Romania	Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca	Cluj-Napoca	Cluj
Romania	Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca	Cluj-Napoca
Romania	Spitalul Clinic de Pneumoftiziologie Constanta, Cartier Palazul Mare	Constanta
Romania	Spitalul Clinic Judetean Sibiu, Clinica Medicala	Sibiu
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologoe "Dr. Victor Babes"	Timisoara	Timis
United States	New Horizons Clinical Research	Cincinnati	Ohio
United States	Clinical Research of West Florida	Clearwater	Florida
United States	Health Science Research Center - Asthma & Allergy Associates	Cortland	New York
United States	The Center for Clinical Research, Washington County Hospital	Hagerstown	Maryland
United States	Innovative Research of West Florida	Largo	Florida
United States	Clinical Research Institute of Southern Oregon	Medford	Oregon
United States	Montana Medical Research, Inc.	Missoula	Montana
United States	The Asthma & Allergy Center	Papillion	Nebraska
United States	Spartanburg Medical Research	Spartanburg	South Carolina
United States	Pulmonary Consultants	Tacoma	Washington
United States	Waterbury Pulmonary Associates	Waterbury	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Guatemala,  Honduras,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites.	Baseline up to Day 85 post dose.
Secondary	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)	Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites.	Baseline up to Day 29, Day 57, and Day 85 post dose.
Secondary	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)	Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites.	Baseline up to Day 29, Day 57, and Day 85 post dose.
Secondary	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	Assessment of functional capacity in study participants with chronic obstructive pulmonary disease (COPD) via the 6-minute walk test (6MWT) provided an objective measure of disability. The 6MWT is a practical and objective evaluation of functional exercise capacity. The test measures the distance that a participant can quickly walk on a flat, hard surface in 6 minutes. In order to ensure uniformity among the sites, the specifications of the course for the 6MWT were modified from being 30 meters long with 60-meter laps to be 15 meters long with 30-meter laps to accommodate space limitations encountered at select sites.	Baseline up to Day 85 post dose.
Secondary	Mean Change in Body Weight From Baseline Through Day 99 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease	Measurements of body weight were performed in the morning when the participant had an empty stomach (ie, had consumed no food overnight) and had emptied the bladder and had a bowel movement, if possible. These measurements were performed using the same calibrated scale for an individual participant throughout study.	Baseline up to Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85, and Day 99 post dose.
Secondary	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	Lean body mass was assessed based on whole-body dual-energy x-ray absorptiometry (DXA).	Baseline up to Day 29, Day 85, and Day 99 post dose.
Secondary	Absolute Concentrations of SUN11031 Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease	Absolute concentrations of SUN11031 in participant plasma samples were measured. When participants were randomly assigned into 1 of 3 treatment groups at baseline, they were also randomly assigned into 1 of 2 sequences in the pharmacokinetic (PK) sparse sampling schedule based on the randomization number.	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.
Secondary	Absolute Concentrations of SUN11031 Metabolites Desacyl-ghrelin Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease	Absolute concentrations of SUN11031 metabolites desacyl-ghrelin in participant plasma samples were measured. When participants were randomly assigned into 1 of 3 treatment groups at baseline, they were also randomly assigned into 1 of 2 sequences in the pharmacokinetic (PK) sparse sampling schedule based on the randomization number.	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.
Secondary	Treatment Emergent Adverse Events Reported in = 2% of Participants Following Treatment With SUN11031 in Participants Having Cachexia Associated With Chronic Obstructive Pulmonary Disease	Treatment-emergent adverse events (TEAEs) were defined as adverse events (AEs) that occurred from the time treatment was administered at Day 1 through the last follow-up visit or a worsening of a pre-existing condition.	Baseline up to Day 113 post dose, up to a total of 134 days.

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