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Pioglitazone for Oral Premalignant Lesions

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ClinicalTrials.gov Identifier: NCT00951379
Recruitment Status : Terminated (Due to slow accrual.)
First Posted : August 4, 2009
Results First Posted : April 6, 2016
Last Update Posted : April 6, 2016
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Oral Leukoplakia
Interventions Drug: Pioglitazone hydrochloride
Other: placebo
Other: laboratory biomarker analysis
Enrollment 52
Recruitment Details Recruitment Period: first participant accrued July 12, 2010 and the last participant accrued on September 10, 2013. Recruitment done in medical clinic settings across the United States, at the European Institute of Oncology in Milan, Italy, and at the BC Cancer Center, Vancouver, British Columbia, Canada.
Pre-assignment Details Of the 99 participants screened during recruitment phase, 47 participants failed screening and were excluded from the trial before assignment to groups. Due to slow accrual, the study was terminated in September 2013.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks Three (3) placebo capsules by mouth once daily for 24 weeks
Period Title: Overall Study
Started 27 25
Completed 21 23
Not Completed 6 2
Reason Not Completed
Adverse Event             4             1
Withdrawal by Subject             1             0
Noncompliance             1             0
Disease Progression             0             1
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo) Total
Hide Arm/Group Description Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks Three (3) placebo capsules by mouth once daily for 24 weeks Total of all reporting groups
Overall Number of Baseline Participants 27 25 52
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants 25 participants 52 participants
59.9  (8.3) 59.0  (10.3) 59.5  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
Female
16
  59.3%
12
  48.0%
28
  53.8%
Male
11
  40.7%
13
  52.0%
24
  46.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
Hispanic or Latino
2
   7.4%
1
   4.0%
3
   5.8%
Not Hispanic or Latino
25
  92.6%
24
  96.0%
49
  94.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   7.4%
1
   4.0%
3
   5.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
25
  92.6%
24
  96.0%
49
  94.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
United States 23 22 45
Italy 4 3 7
Alcohol Use at Baseline   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
Heavy 2 3 5
Light 17 17 34
Non-Drinker 8 5 13
[1]
Measure Description: Heavy drinkers are participants who drank every day; Light drinkers are participants who drank on some days; Non-drinkers are former drinkers or those who never drank alcohol.
Smoking Use at Baseline  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
Current 6 6 12
Former 12 7 19
Never 9 12 21
1.Primary Outcome
Title Overall Response <Clinical and Histologic Response Defined as 50% or Greater Reduction in the Sum of the Measured Products of Perpendicular Dimensions of the Target Lesion(s) or Improvement in the Degree of Dysplasia or Hyperplasia>
Hide Description Overall Dichotomized Clinical and Histologic Response defined as 50% or greater reduction in sum of the measured products of perpendicular dimensions of the target lesion(s) or improvement in the degree of dysplasia or hyperplasia where complete (CR) or partial response (PR) in either clinical or histologic outcome assessed according to criteria given recorded as Response or No Response and analyzed as a dichotomous variable. Clinical Response = CR: Disappearance all evidence target & non-target lesions; PR: >/=50% reduction in sum products of diameters all target lesion(s). Non-target lesions may not increase >/=25% in size & no new lesion. Histologic Response = CR: Complete reversal of dysplasia or hyperplasia to normal epithelium in all biopsied lesions. PR: Improvement of degree of dysplasia or hyperplasia in all biopsied lesion(s) from advanced to early, or from early to normal epithelium in some lesions while other biopsied lesions remain stable.
Time Frame Response assessed at Week 24 ±1 Week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description:
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Three (3) placebo capsules by mouth once daily for 24 weeks
Overall Number of Participants Analyzed 26 25
Measure Type: Number
Unit of Measure: participants
Response 12 8
No Response 14 17
2.Primary Outcome
Title Dichotomized Histologic Response (HR): Participant Complete or Partial Response Defined as =/>50% Reduction in the Sum of the Measured Products of Perpendicular Dimensions of the Target Lesion(s) or Improvement in the Degree of Dysplasia or Hyperplasia
Hide Description HR according to criteria & recorded as Response or No Response, analyzed as dichotomous variable. CR: Complete reversal dysplasia/hyperplasia to normal epithelium in all biopsied lesions. PR: Improvement of degree dysplasia/hyperplasia in all biopsied lesion from advanced to early, or from early to normal epithelium in some lesions while other biopsied lesions remain stable. No Change (NC): No change in degree dysplasia/hyperplasia in all biopsied lesions, anything not CR, PR or PD. Progressive Disease (PD): Any increase in severity histology grade any biopsied lesion. Early premalignant lesion: lesion defined high risk, indicated by presence of one: hyperplasia at high-risk sites (dorsal, lateral or ventral tongue, or floor of mouth) ONLY, or mild dysplasia. Advanced premalignant lesion: lesion with presence of one: moderate dysplasia or severe dysplasia (excluding CIS), erythroplakia with hyperplasia or of any severity of dysplasia.
Time Frame Response assessed at Week 24 ±1 Week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description:
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Three (3) placebo capsules by mouth once daily for 24 weeks
Overall Number of Participants Analyzed 26 25
Measure Type: Number
Unit of Measure: participants
Response 2 2
No Response 24 23
3.Primary Outcome
Title Dichotomized Clinical Response: Participant Complete or Partial Response Defined as =/>50% Reduction in the Sum of the Measured Products of Perpendicular Dimensions of the Target Lesion(s) or Improvement in the Degree of Dysplasia or Hyperplasia
Hide Description Clinical Response assessed according to criteria & recorded as Response or No Response, analyzed as dichotomous variable. Complete Response (CR): Disappearance of all evidence of target AND non-target lesions. Partial Response (PR): greater than or equal to 50% reduction in the sum of the products of diameters of all target lesion(s). Non-target lesions may not increase greater than or equal 25% in size and no new lesion may appear. No Change (NC): No change in the size of the lesion(s) and no new lesions appearing, i.e. anything that is not CR, PR or PD. Progressive Disease (PD): Any increase greater than or equal to 25% in the product of the diameters of any measurable lesions or in the estimated size of non-measurable lesions or the appearance of an unequivocal new lesion.
Time Frame Response assessed at Week 24 ±1 Week
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis includes all participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description:
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Three (3) placebo capsules by mouth once daily for 24 weeks
Overall Number of Participants Analyzed 26 25
Measure Type: Number
Unit of Measure: participants
Response 11 8
No Response 15 17
4.Secondary Outcome
Title Number of Participants With >5.0 mg/L in Level of C-reactive Protein in Plasma
Hide Description

Degree of change of C-reactive protein (CRP) in plasma serum via blood tests.

The longitudinal regression models for analysis of the change in CRP in plasma used, with suitable transformation if necessary to satisfy the model assumptions, with treatment, stage and biomarker value at screening visit as covariates.

Time Frame Baseline to end of study, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pioglitazone's 26 had 24 evaluable specimens at baseline & 20 evaluable at end of study with 2 of those not available for CRP>5 baseline measure: Placebo's 25 had 25 evaluable specimens at baseline & 21 at end of study. Analysis based on specimen viability/availability, no exclusions made for other reasons, participant needed 1/+ dose of treatment.
Arm/Group Title Pioglitazone: CRP>5 at Baseline Pioglitazone: CRP>5 End of Study Placebo: CRP> 5 Baseline Placebo: CRP>5 End of Study
Hide Arm/Group Description:
Measure at baseline, followed by Pioglitazone treatment three 15 mg capsules orally/day for 24 weeks
Measure at end of Pioglitazone treatment, approximately 24 weeks
Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks
Measure at end of Placebo treatment, approximately 24 weeks
Overall Number of Participants Analyzed 24 20 25 21
Measure Type: Number
Unit of Measure: participants
Yes 6 1 4 4
No 18 19 21 17
5.Secondary Outcome
Title Number of Participants With Level of C-reactive Protein in Plasma Decrease From >5.0 mg/L to <= 5.0 mg/L From Baseline to End of Study
Hide Description The longitudinal regression models for analysis of the change in CRP in plasma will be used, with suitable transformation if necessary to satisfy the model assumptions, with treatment, stage and biomarker value at screening visit as covariates.
Time Frame Baseline to end of study, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pioglitazone's 26 had 20 evaluable specimens at baseline & 20 at end of study with 2 of those not available for the CRP>5 baseline measure & Placebo's 25 had 25 evaluable at baseline & 21 evaluable at end of study. Analysis based on specimen viability/availability, no exclusions made for other reasons, participants needed 1/+ dose of treatment.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description:
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Three (3) placebo capsules by mouth once daily for 24 weeks
Overall Number of Participants Analyzed 18 21
Measure Type: Number
Unit of Measure: participants
Yes 3 0
No 15 21
6.Secondary Outcome
Title Number of Participant With Clinical Response by Baseline Characteristics: Tobacco Use
Hide Description Tobacco use summarized by treatment stratified by stage and by group. In addition, the effects of tobacco and alcohol use on the primary endpoint of clinical response assessed.
Time Frame Up to 26 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis includes all participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description:
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Three (3) placebo capsules by mouth once daily for 24 weeks
Overall Number of Participants Analyzed 26 25
Measure Type: Number
Unit of Measure: participants
Never Smoked 4 5
Former Smoker 5 2
Current Smoker 2 1
7.Secondary Outcome
Title Number of Participant With Clinical Response by Baseline Characteristics: Alcohol Use
Hide Description Alcohol use will be summarized by treatment stratified by stage and by group. In addition, the effects of tobacco and alcohol use on the primary endpoint of clinical and pathological response assessed using statistical regression models in an exploratory fashion. Heavy drinkers are participants who drank every day; Light drinkers are participants who drank on some days; Non-drinkers are former drinkers or those who never drank alcohol.
Time Frame Up to 26 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of treatment. One participant in the Pioglitazone arm never received study drug.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description:
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Three (3) placebo capsules by mouth once daily for 24 weeks
Overall Number of Participants Analyzed 26 25
Measure Type: Number
Unit of Measure: participants
Non-Drinker 2 2
Light Drinker 8 6
Heavy Drinker 1 0
8.Secondary Outcome
Title Number of Participants Affected by Adverse Events Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4.0)
Hide Description All adverse events (including serious) and clinical laboratory toxicity summarized affected organ system. Reporting based on the NCI CTCAE v4.0 by treatment, details included in later Adverse Event Module of results.
Time Frame Up to 26 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Population includes all enrolled participants.
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description:
Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks
Three (3) placebo capsules by mouth once daily for 24 weeks
Overall Number of Participants Analyzed 27 25
Measure Type: Number
Unit of Measure: participants
Blood & Lymphatic System Disorders 1 0
Cardiac Disorders 3 2
Ear & Labyrinth Disorders 0 2
Eye Disorders 7 2
Gastrointestinal Disorders 23 22
General Disorders & Administration Site Conditions 12 10
Infections and Infestations 9 8
Injury, Poisoning and Procedural Complications 0 2
Investigations 3 2
Metabolism and Nutrition Disorders 2 0
Musculoskeletal and Connective Tissue Disorders 7 8
Neoplasms Benign, Malignant and Unspecified 1 0
Nervous System Disorders 14 7
Psychiatric Disorders 3 1
Reproductive System and Breast Disorders 1 0
Respiratory, Thoracic and Mediastinal Disorders 18 9
Skin and Subcutaneous Tissue Disorders 4 2
Surgical and Medical Procedures 2 3
Vascular Disorders 5 12
9.Secondary Outcome
Title Biomarker Measurements at Scheduled Visits: Tissue Levels of Cyclin D1
Hide Description Tissue levels of Cyclin D1 as indirect measures of pharmacological effect assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.
Time Frame Baseline to end of study, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two participants in the Pioglitazone arm were not analyzed for Cyclin D1 end of study score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason.
Arm/Group Title Pioglitazone: Baseline Pioglitazone: End of Study Placebo: Baseline Placebo: End of Study
Hide Arm/Group Description:
Measure at baseline, followed by Pioglitazone treatment three 15 mg capsules orally/day for 24 weeks
Measure at end of Pioglitazone treatment, approximately 24 weeks
Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks
Measure at end of Placebo treatment, approximately 24 weeks
Overall Number of Participants Analyzed 25 23 24 24
Mean (Standard Deviation)
Unit of Measure: percentage of staining cells positive
15.5  (10.0) 12.7  (6.9) 12.8  (7.9) 12.9  (7.0)
10.Secondary Outcome
Title Biomarker Measurements at Scheduled Visits: Tissue Levels of Ki-67
Hide Description Tissue levels of Ki-67 for proliferation assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.
Time Frame Baseline to end of study, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Four participants in the Pioglitazone arm were not analyzed for Ki-67 end of study score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason.
Arm/Group Title Pioglitazone: Baseline Pioglitazone: End of Study Placebo: Baseline Placebo: End of Study
Hide Arm/Group Description:
Measure at baseline, followed by Pioglitazone treatment three 15 mg capsules orally/day for 24 weeks
Measure at end of Pioglitazone treatment, approximately 24 weeks
Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks
Measure at end of Placebo treatment, approximately 24 weeks
Overall Number of Participants Analyzed 25 21 24 24
Mean (Standard Deviation)
Unit of Measure: percentage of staining cells positive
9.2  (4.6) 8.9  (4.2) 10.7  (6.5) 8.2  (4.6)
11.Secondary Outcome
Title Biomarker Measurements at Scheduled Visits: Tissue Levels of p21
Hide Description Tissue levels of p21 as indirect measures of pharmacological effect assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.
Time Frame Baseline to end of study, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two participants in the Pioglitazone arm were not analyzed for p21 end of study score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason.
Arm/Group Title Pioglitazone: Baseline Pioglitazone: End of Study Placebo: Baseline Placebo: End of Study
Hide Arm/Group Description:
Measure at baseline, followed by Pioglitazone treatment three 15 mg capsules orally/day for 24 weeks
Measure at end of Pioglitazone treatment, approximately 24 weeks
Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks
Measure at end of Placebo treatment, approximately 24 weeks
Overall Number of Participants Analyzed 25 23 24 24
Mean (Standard Deviation)
Unit of Measure: percentage of staining cells positive
18.7  (10.2) 19.3  (10.6) 17.7  (10.8) 15.6  (7.4)
12.Secondary Outcome
Title Biomarker Measurements at Scheduled Visits: Tissue Levels of B-cell Lymphoma 2 (Bcl2)
Hide Description Tissue levels of Bcl2 as indirect measures of pharmacological effect assessed by immunohistochemistry (IHC). Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported a percentage of cells staining positive, according to nuclear or cytoplasmic compartments.
Time Frame Baseline to end of study, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Four participants of 25 overall in the Pioglitazone arm were not analyzed for Bcl2 end of study score and one participant in Placebo was not analyzed for Bcl2 baseline score. Analysis is based on specimen viability/availability. No exclusions are made for any other reason.
Arm/Group Title Pioglitazone: Baseline Pioglitazone: End of Study Placebo: Baseline Placebo: End of Study
Hide Arm/Group Description:
Measure at baseline, followed by Pioglitazone treatment three 15 mg capsules orally/day for 24 weeks
Measure at end of Pioglitazone treatment, approximately 24 weeks
Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks
Measure at end of Placebo treatment, approximately 24 weeks
Overall Number of Participants Analyzed 25 21 23 24
Mean (Standard Deviation)
Unit of Measure: percentage of staining cells positive
2.8  (3.2) 2.3  (2.3) 4.2  (5.0) 4.6  (8.3)
13.Secondary Outcome
Title Biomarker Measurements at Scheduled Visits: Tissue Levels of PPARG Nucleus and PPARG Cytoplasm
Hide Description Tissue levels of Peroxisome proliferator-activated receptor gamma (PPARG) Nucleus and PPARG Cytoplasm as indirect measures of pharmacological effect, PPAR gamma assessed by immunohistochemistry. Tissue levels of biomarkers assessed from the biopsy obtained at the Screening Clinic Visit and Week 24 ± 1 Week, and plasma levels of biomarkers assessed from blood collected at the Baseline Clinic Visit and Week 24 ± 1 Week. Data reported as percentage of cells staining positive, according to nuclear or cytoplasmic compartments.
Time Frame Baseline to end of study, 24 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Four participants in the Pioglitazone arm were not analyzed at end of study, and two participants in Placebo were not analyzed for PPARG baseline scores. Analysis is based on specimen viability/availability. No exclusions are made for any other reason.
Arm/Group Title Pioglitazone: Baseline Pioglitazone: End of Study Placebo: Baseline Placebo: End of Study
Hide Arm/Group Description:
Measure at baseline, followed by Pioglitazone treatment three 15 mg capsules orally/day for 24 weeks
Measure at end of Pioglitazone treatment, approximately 24 weeks
Measure at baseline, followed by Placebo treatment three capsules orally/day for 24 weeks
Measure at end of Placebo treatment, approximately 24 weeks
Overall Number of Participants Analyzed 25 21 22 24
Mean (Standard Deviation)
Unit of Measure: percentage of staining cells positive
PPARG Nucleus 10.8  (15.7) 7.3  (7.5) 12.4  (10.4) 6.8  (7.2)
PPARG Cytoplasm 21.7  (25.8) 23.5  (28.0) 20.2  (29.9) 21.5  (31.3)
Time Frame Adverse signs and symptoms recorded at each clinic visit beginning week 4 through week 24 (± 1 week). All adverse events followed according to established standards of care. Overall study period: May 2010 to March 2014.
Adverse Event Reporting Description Study source vocabulary for the study began as CTCAE version 3.0 and was translated to version 4.0.
 
Arm/Group Title Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Hide Arm/Group Description Three (3) Pioglitazone 15 mg capsules by mouth once daily for 24 weeks Three (3) placebo capsules by mouth once daily for 24 weeks
All-Cause Mortality
Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/27 (11.11%)      1/25 (4.00%)    
Cardiac disorders     
heart failure  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Infections and infestations     
sepsis  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
squamous cell carcinoma of the tongue  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Surgical and medical procedures     
laparoscopic hysterectomy  1 [1]  1/27 (3.70%)  1 0/25 (0.00%)  0
Pre-existing abdominal aortic aneurysm  1 [2]  0/27 (0.00%)  0 1/25 (4.00%)  1
Vascular disorders     
right femoral artery occlusion  1  0/27 (0.00%)  0 1/25 (4.00%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[1]
Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy, sacrocolpopexy and midurethral tissue fixation system sling
[2]
hospitalization for repair of pre-existing abdominal aortic aneurysm
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Arm I (Pioglitazone Hydrochloride) Arm II (Placebo)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/27 (81.48%)      24/25 (96.00%)    
Blood and lymphatic system disorders     
anemia  1  1/27 (3.70%)  2 0/25 (0.00%)  0
Cardiac disorders     
palpitations  1  2/27 (7.41%)  2 0/25 (0.00%)  0
Ear and labyrinth disorders     
hearing issues  1  0/27 (0.00%)  0 1/25 (4.00%)  1
hearing loss, earwax  1  0/27 (0.00%)  0 1/25 (4.00%)  1
Eye disorders     
bilateral burning eye  1  0/27 (0.00%)  0 1/25 (4.00%)  1
blurred vision  1  1/27 (3.70%)  1 1/25 (4.00%)  1
conjunctival abrasion  1  1/27 (3.70%)  1 0/25 (0.00%)  0
conjunctivitis  1  1/27 (3.70%)  1 0/25 (0.00%)  0
myopia  1  1/27 (3.70%)  1 0/25 (0.00%)  0
red bloodshot eyes  1  1/27 (3.70%)  1 0/25 (0.00%)  0
scotoma of right eye  1  1/27 (3.70%)  1 0/25 (0.00%)  0
vitreous detachment of left eye  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Gastrointestinal disorders     
abdominal pain  1  0/27 (0.00%)  0 1/25 (4.00%)  1
constipation  1  0/27 (0.00%)  0 2/25 (8.00%)  2
diarrhea  1  1/27 (3.70%)  1 1/25 (4.00%)  1
dry mouth  1  3/27 (11.11%)  3 1/25 (4.00%)  1
dyspepsia  1  0/27 (0.00%)  0 1/25 (4.00%)  1
gastritis  1  1/27 (3.70%)  1 0/25 (0.00%)  0
gastrointestinal pain  1  1/27 (3.70%)  1 0/25 (0.00%)  0
hemorrhoids  1  1/27 (3.70%)  1 0/25 (0.00%)  0
lump under tongue  1  1/27 (3.70%)  1 0/25 (0.00%)  0
lip pain  1  0/27 (0.00%)  0 1/25 (4.00%)  1
mucositis oral  1  0/27 (0.00%)  0 2/25 (8.00%)  2
nausea  1  2/27 (7.41%)  2 3/25 (12.00%)  4
oral dysesthesia  1  1/27 (3.70%)  1 0/25 (0.00%)  0
oral hemorrhage  1  0/27 (0.00%)  0 1/25 (4.00%)  1
oral pain  1  6/27 (22.22%)  11 4/25 (16.00%)  4
periodontal disease  1  0/27 (0.00%)  0 1/25 (4.00%)  1
rectal hemorrhage  1  0/27 (0.00%)  0 1/25 (4.00%)  1
striations on tongue  1  1/27 (3.70%)  1 0/25 (0.00%)  0
red spots right lower lip  1  1/27 (3.70%)  1 0/25 (0.00%)  0
stomach pain  1  0/27 (0.00%)  0 1/25 (4.00%)  1
toothache  1  1/27 (3.70%)  1 1/25 (4.00%)  1
vomiting  1  3/27 (11.11%)  3 1/25 (4.00%)  1
General disorders     
edema limbs  1  2/27 (7.41%)  2 2/25 (8.00%)  2
facial pain  1  1/27 (3.70%)  1 1/25 (4.00%)  1
fatigue  1  3/27 (11.11%)  3 4/25 (16.00%)  5
flu like symptoms  1  2/27 (7.41%)  2 1/25 (4.00%)  1
malaise  1  2/27 (7.41%)  2 1/25 (4.00%)  1
non-cardiac chest pain  1  0/27 (0.00%)  0 1/25 (4.00%)  1
sluggishness  1  1/27 (3.70%)  1 0/25 (0.00%)  0
suddenly famished  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Infections and infestations     
bladder infection  1  0/27 (0.00%)  0 1/25 (4.00%)  1
bronchial infection  1  1/27 (3.70%)  1 0/25 (0.00%)  0
toe infection  1  0/27 (0.00%)  0 1/25 (4.00%)  1
lip infection  1  0/27 (0.00%)  0 1/25 (4.00%)  1
lung infection  1  1/27 (3.70%)  1 1/25 (4.00%)  1
sinusitis  1  1/27 (3.70%)  1 1/25 (4.00%)  1
skin infection  1  1/27 (3.70%)  1 0/25 (0.00%)  0
soft tissue infection  1  0/27 (0.00%)  0 1/25 (4.00%)  1
thrush in throat  1  1/27 (3.70%)  1 0/25 (0.00%)  0
tooth infection  1  0/27 (0.00%)  0 1/25 (4.00%)  1
upper respiratory infection  1  2/27 (7.41%)  2 1/25 (4.00%)  1
urinary tract infection  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Injury, poisoning and procedural complications     
fall  1  0/27 (0.00%)  0 1/25 (4.00%)  1
fracture  1  0/27 (0.00%)  0 1/25 (4.00%)  1
Investigations     
alanine aminotransferase (ALT) Increased  1  0/27 (0.00%)  0 1/25 (4.00%)  1
creatinine increased  1  1/27 (3.70%)  1 0/25 (0.00%)  0
weight gain  1  1/27 (3.70%)  1 0/25 (0.00%)  0
weight loss  1  1/27 (3.70%)  1 1/25 (4.00%)  1
Metabolism and nutrition disorders     
hypoglycemia  1  1/27 (3.70%)  1 0/25 (0.00%)  0
increased chloride  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Musculoskeletal and connective tissue disorders     
arms burning sensaton  1  0/27 (0.00%)  0 1/25 (4.00%)  1
arthralgia  1  0/27 (0.00%)  0 2/25 (8.00%)  2
back pain  1  2/27 (7.41%)  2 2/25 (8.00%)  2
mild leg cramps at night  1  1/27 (3.70%)  1 0/25 (0.00%)  0
muscle pain right hip  1  1/27 (3.70%)  1 0/25 (0.00%)  0
myalgia  1  0/27 (0.00%)  0 1/25 (4.00%)  1
neck pain  1  1/27 (3.70%)  1 0/25 (0.00%)  0
pain in extremity  1  1/27 (3.70%)  1 1/25 (4.00%)  1
rotator cuff trauma resulting from a fall  1  0/27 (0.00%)  0 1/25 (4.00%)  1
superficial soft tissue fibrosis  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Nervous system disorders     
dizziness  1  3/27 (11.11%)  3 2/25 (8.00%)  2
dysgeusia  1  1/27 (3.70%)  1 0/25 (0.00%)  0
headache  1  5/27 (18.52%)  7 2/25 (8.00%)  2
hypersomnia  1  0/27 (0.00%)  0 1/25 (4.00%)  1
paresthesia  1  2/27 (7.41%)  2 0/25 (0.00%)  0
sinus pain  1  1/27 (3.70%)  1 1/25 (4.00%)  1
somnolence  1  1/27 (3.70%)  1 0/25 (0.00%)  0
tremor  1  1/27 (3.70%)  1 1/25 (4.00%)  2
Psychiatric disorders     
anxiety  1  2/27 (7.41%)  2 0/25 (0.00%)  0
insomnia  1  1/27 (3.70%)  1 1/25 (4.00%)  1
Reproductive system and breast disorders     
pelvic pain  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
allergic rhinitis  1  2/27 (7.41%)  5 0/25 (0.00%)  0
bronchospasm  1  1/27 (3.70%)  1 0/25 (0.00%)  0
cough  1  3/27 (11.11%)  3 4/25 (16.00%)  4
dry nasal passages  1  1/27 (3.70%)  1 0/25 (0.00%)  0
dyspnea  1  1/27 (3.70%)  1 1/25 (4.00%)  1
epistaxis  1  1/27 (3.70%)  1 0/25 (0.00%)  0
hoarseness  1  0/27 (0.00%)  0 1/25 (4.00%)  1
nasal congestion  1  1/27 (3.70%)  1 1/25 (4.00%)  1
productive cough  1  1/27 (3.70%)  1 0/25 (0.00%)  0
sinus disorder  1  1/27 (3.70%)  1 0/25 (0.00%)  0
slight metallic smell  1  1/27 (3.70%)  2 0/25 (0.00%)  0
sore throat  1  4/27 (14.81%)  5 1/25 (4.00%)  1
tonsillitis  1  0/27 (0.00%)  0 1/25 (4.00%)  1
wheezing  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Skin and subcutaneous tissue disorders     
bee sting  1  1/27 (3.70%)  1 0/25 (0.00%)  0
pruritus  1  1/27 (3.70%)  1 0/25 (0.00%)  0
rash maculo-papular  1  1/27 (3.70%)  2 0/25 (0.00%)  0
skin dyschromia of arms  1  0/27 (0.00%)  0 1/25 (4.00%)  1
small non-painful reddened area lower left arm  1  0/27 (0.00%)  0 1/25 (4.00%)  1
keratotic horns on head  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Surgical and medical procedures     
molar extracted due to failed root canal  1  0/27 (0.00%)  0 1/25 (4.00%)  1
outpatient surgery, knee meniscus repair  1  0/27 (0.00%)  0 1/25 (4.00%)  1
trans oral surgery  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Vascular disorders     
hypertension  1  4/27 (14.81%)  6 11/25 (44.00%)  14
minor venous insufficiency of the legs  1  1/27 (3.70%)  1 0/25 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: University of Texas MD Anderson Phase I/II Prevention Consortium
Organization: University of Texas (UT) MD Anderson Cancer Center
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00951379     History of Changes
Other Study ID Numbers: NCI-2012-03152
NCI-2012-03152 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
UWI H-2009-0106
MDA-2009-0339 ( Other Identifier: MD Anderson Cancer Center (MDACC) )
INC07-10-01 ( Other Identifier: DCP )
N01CN35159 ( U.S. NIH Grant/Contract )
N01CN35153 ( U.S. NIH Grant/Contract )
P30CA016672 ( U.S. NIH Grant/Contract )
First Submitted: July 31, 2009
First Posted: August 4, 2009
Results First Submitted: October 20, 2015
Results First Posted: April 6, 2016
Last Update Posted: April 6, 2016