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Trial record 36 of 53 for:    Orange B

A Single Dose Study of the Safety, Blood Levels and Biological Effects of Aes-103 Compared to Placebo in Subjects With Stable Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT01597401
Recruitment Status : Completed
First Posted : May 14, 2012
Last Update Posted : January 8, 2018
Sponsor:
Collaborators:
SAIC-Frederick, Inc.
Therapeutics for Rare and Neglected Diseases (TRND)
QS Pharma
National Chung Cheng University
Infrared Imaging and Thermometry Unit, Biomedical Engineering and Physical Science Shared Resource (NIBIB)
ClinPharm Consulting, LLC
Ricerca Biosciences LLC
National Heart, Lung, and Blood Institute (NHLBI)
Cato Research
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Tracking Information
First Submitted Date  ICMJE April 26, 2012
First Posted Date  ICMJE May 14, 2012
Last Update Posted Date January 8, 2018
Actual Study Start Date  ICMJE May 12, 2012
Actual Primary Completion Date June 7, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2012)
Safety, as assessed by frequency and severity of adverse events (AEs), and changes in vital signs, 12-lead electrocardiograms (ECGs), and laboratory assessments as compared to baseline. [ Time Frame: 32 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01597401 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2012)
  • Plasma area under the curve (AUC) of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Red blood cell (RBC) hemolysate AUC of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Hemoglobin bound 5-hydroxymethyl-2-furfural (5-HMF) AUC [ Time Frame: predose, .5 hrs, 1 hr, 4 hr, and 12 hr ]
  • Renal elimination of Aes-103 [ Time Frame: predose, 0-4hrs, 4-8hrs, and 8-24hrs ]
  • Percentage of hemoglobin bound to Aes-103 [ Time Frame: predose, 1 hr, 2 hr, 4 hr, and 12 hr ]
  • Change from baseline in resting oxygen saturation (SpO2) [ Time Frame: predose, .5 hrs, 1 hr, 4 hr, and 12 hr ]
  • Change from baseline in partial pressure of oxygen required to achieve 50% hemoglobin saturation (p50) value [ Time Frame: predose, 1 hr, 2 hr, 4 hr, and 12 hr ]
  • Effects of food ingested prior to dosing on plasma AUC of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Percentage of sickled cells under normal ex vivo conditions [ Time Frame: predose, 1 hr, 2 hr, 4 hr, and 12 hr ]
  • Change from baseline in blood flow distribution [ Time Frame: predose and .5 to 2 hr ]
  • Change from baseline in peripheral arterial tonometry [ Time Frame: predose and .5 to 2 hr ]
  • Change from baseline in pain as measured by the Numerical Pain Rating Scale (NPRS) [ Time Frame: -1hr, -.5hrs, -5min, .1hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Plasma maximum concentration (Cmax) of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Plasma time to maximum concentration (Tmax) of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Plasma half life (t1/2) of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Plasma AUC of Aes-103's metabolite, 5-hydroxymethyl-2-furoic acid (HMFA) [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Plasma maximum concentration (Cmax) of HMFA [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Plasma time to maximum concentration (Tmax) of HMFA [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Plasma half life (t1/2) of HMFA [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • RBC hemolysate Cmax of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • RBC hemolysate Tmax of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • RBC hemolysate t1/2 of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • RBC hemolysate AUC of HMFA [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • RBC hemolysate Cmax of HMFA [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • RBC hemolysate Tmax of HMFA [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • RBC hemolysate t1/2 of HMFA [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Hemoglobin bound 5-HMF Cmax [ Time Frame: predose, .5 hrs, 1 hr, 4 hr, and 12 hr ]
  • Hemoglobin bound 5-HMF Tmax [ Time Frame: predose, .5 hrs, 1 hr, 4 hr, and 12 hr ]
  • Hemoglobin bound 5-HMF t1/2 [ Time Frame: predose, .5 hrs, 1 hr, 4 hr, and 12 hr ]
  • Renal elimination of HMFA [ Time Frame: predose, 0-4hrs, 4-8hrs, and 8-24hrs ]
  • Effects of food ingested prior to dosing on plasma Cmax of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Effects of food ingested prior to dosing on plasma Tmax of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Effects of food ingested prior to dosing on plasma t1/2 of Aes-103 [ Time Frame: predose, .1 hrs, .25 hrs, .5 hrs, .75 hrs, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, and 24 hr ]
  • Percentage of sickled cells under hypoxic ex vivo conditions [ Time Frame: predose, 1 hr, 2 hr, 4 hr, and 12 hr ]
  • Change from baseline in vasomotion [ Time Frame: predose and .5 to 2 hr ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Single Dose Study of the Safety, Blood Levels and Biological Effects of Aes-103 Compared to Placebo in Subjects With Stable Sickle Cell Disease
Official Title  ICMJE A Phase 1, Placebo-Controlled, Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Escalating, Single Oral Doses of Aes-103 in Subjects With Stable Sickle Cell Disease
Brief Summary The purpose of this study is to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of Aes-103 (active ingredient 5-hydroxymethyl-2-furfural [5-HMF]) compared with placebo in subjects with stable sickle cell disease (SCD). Safety will be measured by monitoring adverse events (AEs), electrocardiograms (ECGs), vital signs, and laboratory values. Pharmacokinetics of Aes-103 will be measured over time in plasma, red blood cell hemolysate and binding of Aes-103 to hemoglobin. Pharmacodynamic effects will be assessed by measuring partial pressure of oxygen at which 50% of hemoglobin is saturated with oxygen (p50) while breathing normal air, blood oxygen levels (SpO2), ex-vivo antisickling effects in a hypoxic environment, and by imaging related changes in tissue blood flow and oxygen levels.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE
  • Drug: Aes-103
    300 mg Aes-103 powder reconstituted in orange juice to a volume of 100 mL per single dose for oral administration.
  • Drug: Aes-103
    1000 mg Aes-103 powder reconstituted in orange juice to a volume of 100 mL per single dose for oral administration.
  • Drug: Aes-103
    2000 mg Aes-103 powder reconstituted in orange juice to a volume of 100 mL per single dose for oral administration.
  • Drug: Aes-103
    4000 mg Aes-103 powder reconstituted in orange juice to a volume of 100 mL per single dose for oral administration.
  • Drug: Placebo
    Orange juice vehicle, a solution that is highly similar in appearance to the Aes-103 orange juice solution.
Study Arms  ICMJE
  • Experimental: Aes-103 300 mg to 1000 mg (Group A)
    Group A will consist of six subjects receiving a single dose of either a low dose of Aes-103 (300 mg) or placebo without food. After a minimum of a 1- to 2-week washout period and evaluation of blinded safety data, subjects initially randomized to Aes-103 will receive a second, higher dose of Aes-103 (1,000 mg), and subjects initially randomized to placebo will receive a second dose of placebo without food.
    Interventions:
    • Drug: Aes-103
    • Drug: Aes-103
    • Drug: Placebo
  • Experimental: Aes-103 2000 mg to 4000 mg (Group B)
    Group B will consist of six subjects receiving an initial dose of either Aes 103 (2,000 mg) or placebo without food. After a minimum of a 1- to 2-week washout period and evaluation of blinded safety data, subjects initially randomized to Aes-103 will receive a second, higher dose of Aes-103 (4,000 mg), and subjects initially randomized to placebo will receive a second dose of placebo without food.
    Interventions:
    • Drug: Aes-103
    • Drug: Aes-103
    • Drug: Placebo
  • Experimental: Top Dose Expansion (Group C)
    Once the top dose (i.e., highest tolerated) of Aes-103 has been determined, the size of this group will be expanded with an additional six subjects (Group C) for a total of 12 at that dose, distributed so that six subjects receiving hydroxyurea (HU) and six subjects not receiving HU (for the past 6 months) will receive study drug (five receiving Aes-103 and one receiving placebo in each of the HU and non-HU treated cohorts). This total of 12 subjects includes the initial six subjects who received the highest dose in the study plus six Group C subjects. These subjects will receive a single dose of the top dose of Aes-103 or placebo without food. After a minimum of a 1- to 2-week washout period and evaluation of blinded safety data, subjects initially randomized to Aes-103 will receive a second dose of the top dose of Aes-103 and subjects initially randomized to placebo will receive a second dose of placebo; all subjects will be administered a pre-dose, high fat, high protein meal.
    Interventions:
    • Drug: Aes-103
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 25, 2013)
19
Original Estimated Enrollment  ICMJE
 (submitted: May 11, 2012)
24
Actual Study Completion Date  ICMJE June 7, 2013
Actual Primary Completion Date June 7, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Be male or female, aged 18-65 years old, inclusive
  • Have sickle cell disease (SCD) (hemoglobin SS) without hospitalization for pain crises in the 30 days before screening or for any SCD complications on more than two occasions in the past 12 months; subjects are allowed concomitant usage of hydroxyurea (HU) if the dosage is stable for the 2 months before screening and is at a dosage that does not exceed the product's labeling.
  • Have normal laboratory values as defined below:

    • Direct bilirubin 0.1 to 1.0 mg/dL
    • Alanine transaminase (serum glutamic pyruvic transaminase) 6 to 41 IU/L
    • Creatinine for females 0.56 to 1.16 mg/dL and for males 0.77 to 1.19 mg/dL
  • If female, be non-pregnant and non-breastfeeding and be surgically sterile or using an acceptable method of contraception throughout the study and for 30 days after study completion
  • Have successfully completed an outpatient screening visit consisting of medical history, physical examination, 12-lead ECG, vital signs, hematology and chemistry tests, urinalysis, urine drug screen, pregnancy test (females), hemoglobin electrophoresis, hepatitis B and C screening, and HIV serology (Note: Subjects with abnormal screening values may be eligible if the results are not clinically significant, as judged by the investigator or medical monitor)
  • Be able to understand and have provided written informed consent including signature on an informed consent form approved by an institutional review board
  • Agree to abide by the study schedule and dietary restrictions and to return for the required assessments
  • Be willing to abstain from foods high in 5-HMF (e.g., coffee, malt, barley, balsamic vinegar, dried fruits, and caramel products) for at least 3 days before each dosing

Exclusion Criteria:

  • Have evidence of clinically significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, hematological, neurological, psychiatric, or other disease that may interfere with the objectives of the study or the safety of the subject, as judged by the investigator in agreement with the sponsor or medical monitor, or have been hospitalized in the past 6 months as a result of these conditions
  • Have been hospitalized in the 14 days before enrollment, for any reason
  • Be currently on regularly scheduled transfusions
  • Have received a transfusion within 2 weeks of administration of study drug
  • Have taken herbal preparations in the 2 weeks before dosing (Note: subjects are allowed concomitant usage of HU and other scheduled prescription drugs if the dosage is stable for the 2 months before screening and is at a dosage that does not exceed the product's labeling. These scheduled prescription medications will be continued during the study [including during dosing]. All other medications, including over-the-counter medications used according to the product labeling, administered on an as-needed basis will be permitted except for the 24 hour period before dosing and the day of dosing. Medications for pain management will be allowed as needed [including during dosing.])
  • Have taken any other investigational drug within 30 days or 5 half-lives before the screening visit, whichever is longer
  • Consumed more than 14 alcoholic drinks per week or more than 3 drinks per day at any point in the past month
  • Have received disulfiram or 4-methylpyrazole within 30 days before dosing
  • Have taken any cough-cold product containing dextrorphan or dextromethorphan within 4 days before dosing
  • Have positive result for urine drug test (cocaine, marijuana, opiates, amphetamines, methamphetamines, benzodiazepines, ethanol) at screening visit. However, use of opiates, amphetamines, or benzodiazepines is allowed if prescribed by a physician.
  • Have engaged in strenuous exercise within 72 hours prior to dosing
  • Be considered not suitable for participation in this study for any reason, as judged by the investigator
  • Have pre-existing allergic or other adverse reactions to orange juice
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01597401
Other Study ID Numbers  ICMJE Aes-103-002
1ZIAHL006149-01 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shire ( Baxalta now part of Shire )
Study Sponsor  ICMJE Baxalta now part of Shire
Collaborators  ICMJE
  • SAIC-Frederick, Inc.
  • Therapeutics for Rare and Neglected Diseases (TRND)
  • QS Pharma
  • National Chung Cheng University
  • Infrared Imaging and Thermometry Unit, Biomedical Engineering and Physical Science Shared Resource (NIBIB)
  • ClinPharm Consulting, LLC
  • Ricerca Biosciences LLC
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Cato Research
Investigators  ICMJE
Principal Investigator: Brahm Goldstein, MD Shire
PRS Account Shire
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP