The purpose of this study is to evaluate the hemoglobin response (efficacy), safety, and tolerability of orally administered AKB-6548 in participants with Chronic Kidney Disease (pre-dialysis) with anemia with dosing for 20 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
210
Percentage of Participants Achieving a Successful Hemoglobin Response
Hemoglobin (Hgb) response was defined as participants with mean Hgb ≥11.0 grams per deciliter (g/dL) (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving Erythropoiesis-Stimulating Agents (ESA) or transfusion.
Time frame: Weeks 19 and 20
Percentage of Participants With Hemoglobin Value ≥13.0 g/dL at Any Time During the Study
Participants who have experienced an excursion in Hgb to ≥13.0 g/dL at any time during the study were considered as "failures". Data was presented for failures.
Time frame: Up to 20 Weeks
Percentage of Participants Achieving a Successful Hemoglobin Response, Determined Solely Based on the Hemoglobin Value
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing). Analysis of this secondary outcome measure is a reanalysis of the primary outcome measure whereby the response was determined solely by the Hgb value and receiving rescue therapy did not make the participant a failure.
Time frame: Weeks 19 and 20
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Treatment naïve Group
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Treatment Naïve group, defined as participants who had never received treatment with an ESA and who had a screening Hgb level of ≤10.5 g/dL.
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Unnamed facility
Glendale, Arizona, United States
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Tucson, Arizona, United States
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Azusa, California, United States
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Chula Vista, California, United States
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Downey, California, United States
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El Centro, California, United States
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La Mesa, California, United States
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Long Beach, California, United States
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Riverside, California, United States
Unnamed facility
Sacramento, California, United States
...and 37 more locations
Time frame: Weeks 19 and 20
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Previously Treated Group
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Previously Treated group, defined as participants who had previously received ≥1 dose of an ESA, had been off of ESA therapy for ≥11 weeks at the time of screening, and had a screening Hgb level of ≤10.5 g/dL.
Time frame: Weeks 19 and 20
Percentage of Participants Achieving a Successful Hemoglobin Response in ESA Actively Treated Group
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Participants were assigned to 1 of 3 study groups based on their ESA status at the screening visit: Naïve, Previously Treated and Actively Treated. Analysis of this secondary outcome measure was performed in the ESA Actively Treated group, defined as participants who had been actively treated with an ESA for a minimum of 4 months before screening, had received at least 2 doses within the last 4 months, had received their last dose within 6 weeks before screening, and had a screening Hgb level ≥9.5 g/dL and ≤12.0 g/dL.
Time frame: Weeks 19 and 20
Percentage of Participants Achieving a Successful Hemoglobin Response, Analyzed in mITT Population
Hgb response was defined as participants with mean Hgb ≥11.0 g/dL (average of Weeks 19 and 20) or increase in Hgb by ≥ 1.2 g/dL (average of Weeks 19 and 20) over pre-dose average (average of the two Hgb values obtained prior to dosing) without receiving ESA or transfusion. Analysis of this secondary outcome measure was performed in the mITT population.
Time frame: Weeks 19 and 20
Change From Baseline in Hemoglobin
Blood samples were collected to assess Hgb. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hgb concentration increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Absolute Values of Hemoglobin
Blood samples were collected at indicated time points for analysis of hemoglobin
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Change From Baseline in Hematocrit
Blood samples were collected to assess Hematocrit. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated Hematocrit concentration increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Absolute Values of Hematocrit
Blood samples were collected at indicated time points for analysis of Hematocrit.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Change From Baseline in Red Blood Cell Count
Blood samples were collected to assess red blood cell count. Baseline was defined as the mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated red blood cell count increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Absolute Values of Red Blood Cell Count
Blood samples were collected at indicated time points for analysis of red blood cell count.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Change From Baseline in Reticulocyte Count
Blood samples were collected to assess reticulocyte count. Baseline was defined as mean of two samples obtained prior to dosing (Screening and Baseline). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. A positive change from Baseline indicated reticulocyte count increased.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Absolute Values of Reticulocyte Count
Blood samples were collected at indicated time points for analysis of reticulocyte count.
Time frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12, Week 16, Week 19 and Week 20
Percentage of Participants Who Received ESA Rescue
Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Mean Number of ESA Rescue Doses Administered Per Participant
Participants were administered epoetin alfa or darbepoetin alfa as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Percentage of Participants Who Received Packed Red Blood Cell Transfusion Rescue
Participants were administered packed red blood cell transfusion as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia
Time frame: Up to 20 Weeks
Number of Packed Red Blood Cell Transfusion Administered Per Participant
Participants were administered packed red blood cells as a rescue medication who have met the Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Time to First Transfusion or ESA Rescue Medication Intake
Rescue therapy was defined as red blood cell transfusion or ESA administration in participants meeting Hgb rescue criteria in addition to having experienced a clinically significant worsening of their anemia or the symptoms of anemia.
Time frame: Up to 20 Weeks
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (SAEs)
An Adverse Event (AE) was defined as any untoward medical occurrence, signs, symptoms, disease, or laboratory or physiological observations occurring in a participant administered with drug, regardless of a causal relationship with that treatment or usage. This also included all suspected adverse medication reactions, reactions from medication overdose, abuse, withdrawal, sensitivity, toxicity, unrelated illnesses, including worsening a pre-existing condition, injury, or accidents. Serious Adverse Events (SAEs) was defined as any life-threatening condition; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; or death.
Time frame: Up to 20 Weeks
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameter Values
Parameters assessed for laboratory values included hematology, serum chemistry, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to 20 Weeks
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Parameters assessed for vital signs included sitting (at rest for a minimum of 5 minutes) heart rate, respiratory rate, body temperature, and blood pressure. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to 20 Weeks
Number of Participants With Clinically Abnormal 12-Lead Electrocardiogram (ECG) Findings
A standard 12-lead ECG was performed following dosing in a supine position for approximately 10 minutes. ECGs were taken prior to blood draws when possible. The investigator was responsible for reviewing laboratory results for clinical significance.
Time frame: Up to 20 Weeks
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
A Baseline physical examination was performed at screening. Otherwise, abbreviated physical examinations were conducted and were to include heart, lung, and abdomen. The investigator was responsible for reviewing laboratory results for clinically significant changes.
Time frame: Up to 20 Weeks