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

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

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.

Study Overview

• Status: Completed
• Conditions: Cachexia
• Intervention / Treatment: Drug: SUN11031 20 μg/kg; Drug: SUN11031 40 μg/kg; Drug: Placebo comparator

• Study Type: Interventional
• Enrollment (Actual): 227
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Centro de Investigación Médica Lanús
  • Capital Federal, Argentina, C1122AAK
    • FAICEP
  • Capital Federal, Argentina, C1425AWC
    • Instituto Médico de Asistencia e Investigación
  • Capital Federal, Argentina, C1426ABP
    • Centro Médico Dra. De Salvo
  • Capital Federal, Argentina, C1429BNQ
    • Centro Médico Belgrano
  • Capital Federal, Argentina
    • Centro Ceri
  • Capital Federal, Argentina
    • Centro de Estudios Neumonologicos
  • Mendoza, Argentina, cp 5500
    • Fuesmen
  • Mendoza, Argentina
    • Instituto de Enfermedades Respiratorias
  • Paraná, Argentina
    • Centro de Medicina Respiratoria
  • Tucuman, Argentina
    • Instituto de Patologia Respiratoria
  • Buenos Aires
    • Florencío Varela, Buenos Aires, Argentina
      • Centro de Investigaciones Médicas
    • Mar del Plata, Buenos Aires, Argentina
      • Instituto de Investigaciones Clinicas Mar del Plata
    • Quilmes, Buenos Aires, Argentina, B1878FNR
      • Centro Respiratorio Quilmes
  • Río Negro
    • Cipolletti, Río Negro, Argentina, R8324EMD
      • Instituto de Investigaciones Clinicas Cipolletti
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DBS
      • Clinica del Tórax
    • Rosario, Santa Fe, Argentina, S2000DSV
      • Instituto Cardiovascular de Rosario
  • Tucumán
    • San Miguel de Tucumán, Tucumán, Argentina
      • CEMIT
• Chile
  • Santiago, Chile
    • Hospital Barros Luco Trudeau
  • Santiago, Chile
    • Hospital San José
  • Santiago, Chile
    • Integramedica La Florida
• Guatemala
  • Guatemala, Guatemala, 01010
    • Instituto Pneos
  • Guatemala, Guatemala
    • Edificio Centro Medico II
  • Guatemala, Guatemala
    • Private Clinic
  • Quetzaltenango, Guatemala
    • Edificio Medico San Lucas
• Honduras
  • San Pedro Sula, Honduras
    • Centro de Neumologia y Alergia
  • Tegucigalpa, Honduras
    • Instituto Nacional Cardiopulmonar
• Romania
  • Cluj-Napoca, Romania, 400371
    • Spitalul Clinic De Pneumoftiziologie "Leon Daniello" Cluj-Napoca
  • Constanţa, Romania, 900002
    • Spitalul Clinic de Pneumoftiziologie Constanta, Cartier Palazul Mare
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean Sibiu, Clinica Medicala
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400371
      • Spitalul Clinic De Pneumoftiziologie "Leon Daniello" Cluj-Napoca
  • Timiş
    • Timişoara, Timiş, Romania, 300310
      • Spitalul Clinic de Boli Infectioase si Pneumoftiziologoe "Dr. Victor Babes"
• United States
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Waterbury Pulmonary Associates
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Largo, Florida, United States, 33756
      • Innovative Research of West Florida
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • The Center for Clinical Research, Washington County Hospital
  • Montana
    • Missoula, Montana, United States, 59808
      • Montana Medical Research, Inc.
  • Nebraska
    • Papillion, Nebraska, United States, 68046
      • The Asthma & Allergy Center
  • New York
    • Cortland, New York, United States, 13045
      • Health Science Research Center - Asthma & Allergy Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45252
      • New Horizons Clinical Research
  • Oregon
    • Medford, Oregon, United States, 97504
      • Clinical Research Institute of Southern Oregon
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Washington
    • Tacoma, Washington, United States, 98405
      • Pulmonary Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; SUN11031 for injection, low dose, twice daily for 12 weeks	Drug: SUN11031 20 μg/kg; Twice daily subcutaneous injections of SUN11031 20 μg/kg for 12 weeks.
EXPERIMENTAL: Group 2; SUN11031 for injection, higher dose, twice daily for 12 weeks	Drug: SUN11031 40 μg/kg; Twice daily subcutaneous injections of SUN11031 40 μg/kg for 12 weeks.
PLACEBO_COMPARATOR: Group 3; Placebo injection, twice daily for 12 weeks	Drug: Placebo comparator; Twice daily subcutaneous injections of placebo for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 15, 2008
• Primary Completion (ACTUAL): October 8, 2009
• Study Completion (ACTUAL): October 8, 2009

Study Registration Dates

• First Submitted: May 1, 2008
• First Submitted That Met QC Criteria: June 13, 2008
• First Posted (ESTIMATE): June 17, 2008

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Cachexia, COPD, Chronic Obstructive Pulmonary Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Respiratory Tract Diseases; Nutrition Disorders; Body Weight; Body Weight Changes; Emaciation; Weight Loss; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Wasting Syndrome; Cachexia
• Other Study ID Numbers: ASBI 307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No