Clinical Trial: 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

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 Summary:
Sponsor: Baxalta US Inc.

Current Primary Outcome: 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: Same as current

Current Secondary Outcome:

  • 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 [ T

    Original Secondary Outcome: Same as current

    Information By: Baxalta US Inc.

    Dates:
    Date Received: April 26, 2012
    Date Started: May 2012
    Date Completion:
    Last Updated: August 6, 2015
    Last Verified: August 2015