Trial Outcomes & Findings for Oral Cyclosporine in Chronic Obstructive Pulmonary Disease (NCT NCT00974142)

NCT ID: NCT00974142

Last Updated: 2025-06-25

Results Overview

Measurement of nephrotoxicity by monitoring serum creatinine over 16 week treatment interval. Mean serum creatinine values were assessed at Week 2, 4, 6, 8, 10, 12 and 16. The mean values of all measurements for each participant were calculated and then the mean across participants was calculated. Values expressed as mean ± SD.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 43 participants
• Primary outcome timeframe: 16 weeks
• Results posted on: 2025-06-25

Participant Flow

Patients were recruited from local clinics, advertisement, and a disease specific registry

772 patients underwent initial screening and 43 were eligible to sign consent. These patients underwent a second 2 week screening process and 17 subjects met all criteria for randomization

Participant milestones

Measure	Cyclosporine Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo Randomized to placebo capsules identical in appearance to cyclosporine
Overall Study STARTED	8	9
Overall Study COMPLETED	8	9
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Oral Cyclosporine in Chronic Obstructive Pulmonary Disease

Baseline characteristics by cohort

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine	Total n=17 Participants Total of all reporting groups
Age, Continuous	68 years n=5 Participants	63 years n=7 Participants	67 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Forced Vital Capacity (%)	88 % predicted n=5 Participants	77 % predicted n=7 Participants	79 % predicted n=5 Participants
Forced Expiratory Volume 1 second (%)	38 % predicted n=5 Participants	43 % predicted n=7 Participants	39 % predicted n=5 Participants
Functional Residual Capacity (%)	146 % predicted n=5 Participants	149 % predicted n=7 Participants	149 % predicted n=5 Participants
Total Lung Capacity (%)	123 % predicted n=5 Participants	119 % predicted n=7 Participants	119 % predicted n=5 Participants
Partial pressure of carbon dioxide (pCO2)	40 mm Hg STANDARD_DEVIATION 3.6 • n=5 Participants	42.6 mm Hg STANDARD_DEVIATION 3.9 • n=7 Participants	41.2 mm Hg STANDARD_DEVIATION 3.7 • n=5 Participants
Partial pressure of oxygen (pO2)	71 mm Hg STANDARD_DEVIATION 11 • n=5 Participants	76 mm Hg STANDARD_DEVIATION 20 • n=7 Participants	74 mm Hg STANDARD_DEVIATION 15 • n=5 Participants
Weight	83 kilograms n=5 Participants	93 kilograms n=7 Participants	84 kilograms n=5 Participants
Systolic blood pressure (mm Hg)	141 mm Hg n=5 Participants	133 mm Hg n=7 Participants	138 mm Hg n=5 Participants
Diastolic blood pressure (mm Hg)	82 mm Hg n=5 Participants	78 mm Hg n=7 Participants	79 mm Hg n=5 Participants
White blood cell count	7.3 x10E ^09/L STANDARD_DEVIATION 1.3 • n=5 Participants	6.6 x10E ^09/L STANDARD_DEVIATION 2.0 • n=7 Participants	7.1 x10E ^09/L STANDARD_DEVIATION 2.2 • n=5 Participants
Hemoglobin	13.7 grams / dL STANDARD_DEVIATION 1.0 • n=5 Participants	13.6 grams / dL STANDARD_DEVIATION 0.9 • n=7 Participants	13.7 grams / dL STANDARD_DEVIATION 1.03 • n=5 Participants
Blood Urea Nitrogen	16 mg / dL STANDARD_DEVIATION 5.4 • n=5 Participants	13 mg / dL STANDARD_DEVIATION 3.2 • n=7 Participants	13.4 mg / dL STANDARD_DEVIATION 3.9 • n=5 Participants
Creatinine	0.9 mg / dL STANDARD_DEVIATION 0.2 • n=5 Participants	0.9 mg / dL STANDARD_DEVIATION 0.2 • n=7 Participants	0.9 mg / dL STANDARD_DEVIATION 0.2 • n=5 Participants
Glucose	102 mg / dL STANDARD_DEVIATION 13 • n=5 Participants	113 mg / dL STANDARD_DEVIATION 29 • n=7 Participants	111 mg / dL STANDARD_DEVIATION 29 • n=5 Participants
Cholesterol	183 mg / dL STANDARD_DEVIATION 30 • n=5 Participants	193 mg / dL STANDARD_DEVIATION 20 • n=7 Participants	183 mg / dL STANDARD_DEVIATION 20 • n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks

Measurement of nephrotoxicity by monitoring serum creatinine over 16 week treatment interval. Mean serum creatinine values were assessed at Week 2, 4, 6, 8, 10, 12 and 16. The mean values of all measurements for each participant were calculated and then the mean across participants was calculated. Values expressed as mean ± SD.

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients- Nephrotoxicity - Measured by Serum Creatinine	0.94 mg / dL Standard Deviation 0.2	0.88 mg / dL Standard Deviation 0.2

PRIMARY outcome

Timeframe: 16 weeks

Development of renal insufficiency defined as > 30% elevation in serum creatinine above baseline which required dose modification of the cyclosporine over 16 week treatment interval at Week 2, 4, 6, 8, 10, 12 and 16. Outcome measured the number of subjects who developed renal insufficiency during the study treatment interval.

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Renal Insufficiency	4 Participants	1 Participants

PRIMARY outcome

Timeframe: 16 weeks

Clinical diagnosis of infection which requires systemic antibiotic therapy during the 16 week study interval at Week 2, 4, 6, 8, 10, 12 and 16. Outcome measured the number of subjects who developed an infection requiring systemic antibiotic therapy during the study treatment interval.

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Safety Profile of Oral Cyclosporin A Immunotherapy in Advanced Stage Chronic Obstructive Pulmonary Disease Patients - Number of Patients That Developed Infection Requiring Systemic Antibiotic Therapy	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 16 weeks

Population: Cyclosporine blood levels were not analyzed in placebo group.

Cyclosporine blood levels on therapy over 16 week treatment interval were measured at Weeks 2, 4, 6, 8, 10, 12 & 16. The median for each participant was found and then the overall median was determined. Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo Randomized to placebo capsules identical in appearance to cyclosporine
Pharmacokinetic - Pharmacodynamic Relationship of Oral Cyclosporine and Biomarkers of an Adaptive Immune Response - Cyclosporine Blood Levels	147 ng/mL Interval 69.0 to 196.0	—

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of cluster of differentiation 4 (CD4) at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 4 (CD4)	-3.1 % of cells expressing biomarkers Interval -18.8 to 3.5	3.6 % of cells expressing biomarkers Interval -8.5 to 45.2

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of peripheral blood T cell biomarkers - cluster of differentiation 8 (CD8), cluster of differentiation 28 (CD28) at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Peripheral Blood T Cell Biomarkers Over 16 Week Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Cluster of Differentiation 28	-0.78 % of cells expressing biomarkers Interval -19.2 to 6.3	-1.6 % of cells expressing biomarkers Interval -6.6 to 3.0

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of peripheral blood cells expressing biomarker - cluster of differentiation 8 (CD8), major histocompatibility complex (MHC) II at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8 and Major Histocompatibility Complex II	-2.4 % of cells expressing biomarkers Interval -11.2 to 7.2	0.5 % of cells expressing biomarkers Interval -4.7 to 3.1

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of peripheral blood T cell biomarkers - CD8+interferon gamma at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Interferon Gamma	-4.1 % of cells expressing biomarkers Interval -24.1 to 49.6	4.4 % of cells expressing biomarkers Interval -44.6 to 51.3

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of peripheral blood T cell biomarkers - cluster of differentiation 4+ interleukin-2 at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 4+ Interleukin-2	-1.7 % of cells expressing biomarkers Interval -13.3 to 16.8	4.7 % of cells expressing biomarkers Interval -15.6 to 11.1

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of peripheral blood T cell biomarkers - CD8+ tumor necrosis factor at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Peripheral Blood T Cell Biomarkers Over Treatment Interval - Change in the Percentage of Cluster of Differentiation 8+ Tumor Necrosis Factor	0.0 % of cells expressing biomarkers Interval -52.6 to 9.8	2.3 % of cells expressing biomarkers Interval -18.0 to 32.3

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of post predicted value of forced vital capacity at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Vital Capacity	-0.01 Percentage of post predicted value Interval -0.04 to 0.6	0.07 Percentage of post predicted value Interval -0.3 to 0.2

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Outcome measured the change in the percentage of post predicted value of forced expiratory volume in 1 second at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Effects of Cyclosporin A on Respiratory Function - Change in the Percentage of Post Predicted Value of Forced Expiratory Volume in 1 Second	-0.02 Percentage of post predicted value Interval -0.3 to 0.3	-0.02 Percentage of post predicted value Interval -0.2 to 0.1

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Measurement of exercise capacity by a shuttle walk distance measured in feet at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). The purpose of the shuttle walk test is to see how far and fast a patient can walk (without stopping for a rest) by following a series of time signals.Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Effects of Cyclosporin A on Respiratory Function - Change in Exercise Capacity by a Shuttle Walk Distance Measured in Feet	230 feet Interval 170.0 to 450.0	220 feet Interval 140.0 to 350.0

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Scores on a shortness of breath scale (University of California at San Diego Dyspnea scale): shortness of breath questionnaire scores are summed as a total score ranging from 0-120 with higher scores indicating more severe breathlessness. Assessments were performed at midpoint assessment (Week 8) and at the conclusion of treatment (Week 16). Values expressed as median (full range).

Outcome measures

Measure	Cyclosporine n=8 Participants Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 Participants Randomized to placebo capsules identical in appearance to cyclosporine
Effects of Cyclosporin A on Symptoms - Change in Scores on a Shortness of Breath Scale	39 units on a scale Interval 10.0 to 81.0	39 units on a scale Interval 4.0 to 85.0

Adverse Events

Cyclosporine

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Cyclosporine n=8 participants at risk Randomized post 2nd level screen to 3 mg/kg / day oral cyclosporine	Placebo n=9 participants at risk Randomized to placebo capsules identical in appearance to cyclosporine
Renal and urinary disorders Renal insufficiency	50.0% 4/8 • Number of events 4 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	11.1% 1/9 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Gastrointestinal disorders Gastrointestinal upset	50.0% 4/8 • Number of events 4 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	0.00% 0/9 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Renal and urinary disorders Hyperkalemia	25.0% 2/8 • Number of events 2 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	0.00% 0/9 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Renal and urinary disorders Hypertension	12.5% 1/8 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	0.00% 0/9 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Nervous system disorders Tremor	12.5% 1/8 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	0.00% 0/9 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Nervous system disorders Muscle cramp	12.5% 1/8 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	0.00% 0/9 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Respiratory, thoracic and mediastinal disorders Respiratory colonization	12.5% 1/8 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	11.1% 1/9 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Respiratory, thoracic and mediastinal disorders Respiratory Infection -Bronchitis	12.5% 1/8 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	11.1% 1/9 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary nodule	0.00% 0/8 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	11.1% 1/9 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/8 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks	11.1% 1/9 • Number of events 1 • Patients received the intervention over 16 weeks but were monitored for a total of 40 weeks

Additional Information

Michael Donahoe MD

University of Pittsburgh Medical Center

Phone: 412-648-9636

Email: donahoem@upmc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place