Efficacy and Safety Study to Evaluate Vadadustat for the Maintenance Treatment of Anemia in Participants With Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
Study Details
Study Description
Brief Summary
A multicenter, randomized, open-label, active-controlled Phase 3 study for the maintenance treatment of anemia in participants with Non-dialysis-dependent Chronic Kidney Disease (NDD-CKD)
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Detailed Description
This is a multicenter, randomized, open-label, active-controlled Phase 3 study of the efficacy and safety of Vadadustat versus Darbepoetin alfa for the maintenance treatment of anemia in participants with NDD-CKD
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Vadadustat
|
Drug: Vadadustat
Oral dose administered once daily for ≥36 weeks. Dose adjustment based on hemoglobin level as defined in the protocol.
Other Names:
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Active Comparator: Darbepoetin alfa
|
Drug: Darbepoetin alfa
Subcutaneous or intravenous dose administered for ≥36 weeks. Initial dose based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) [Baseline; Weeks 24 to 36]
The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates.
- Median Time to First Major Adverse Cardiovascular Event (MACE) [Up to Week 208]
MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
Secondary Outcome Measures
- Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52) [Baseline; Weeks 40 to 52]
The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates.
- Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis [Up to Week 208]
MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
- Median Time to First Cardiovascular MACE [Up to Week 208]
MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
- Median Time to First Cardiovascular Death [Up to Week 208]
Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
- Median Time to First All-cause Mortality [Up to Week 208]
Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure.
Other Outcome Measures
- Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) [Weeks 24 to 36]
- Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) [Weeks 24 to 36]
- Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) [Weeks 40 to 52]
- Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) [Weeks 40 to 52]
- Exploratory - Proportion of Participants With an Hb Increase of >1.0 g/dL From Baseline Visit [Baseline; up to Week 52]
- Exploratory - Time to Achieve Hb Increase of >1.0 g/dL From Baseline Visit [Baseline; up to Week 52]
- Exploratory - Mean Change in Hb Between Baseline (Mean Pretreatment Hb) and the Primary Evaluation Period (Mean Hb From Weeks 24 to 36) Stratified by Pre-baseline Erythropoiesis-stimulating Agent (ESA) Exposure [Baseline; Weeks 24 to 36]
- Exploratory - Mean Monthly Dose of Intravenous (IV) Elemental Iron Administered in Participants Who Have Received IV Iron [Up to Week 52]
- Exploratory - Proportion of Participants Receiving IV Iron Therapy [Up to Week 52]
- Exploratory - Proportion of Participants Receiving Red Blood Cells (RBCs) Transfusion(s) [Up to Week 52]
Eligibility Criteria
Criteria
Inclusion Criteria:
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≥18 years of age
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Diagnosis of chronic kidney disease (CKD) with an estimated glomerular filtration rate ≤60 milliliters per minute per 1.73 square meter (mL/min/1.73 m^2) at Screening and not expected to start dialysis within 6 months of Screening
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Currently maintained on erythropoiesis-stimulating agents therapy, with a dose received within 6 weeks prior to or during Screening
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Mean Screening hemoglobin between 8.0 and 11.0 grams per deciliter (g/dL) (inclusive) in the United States (US) and between 9.0 and 12.0 g/dL (inclusive) outside of the US
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Serum ferritin ≥100 nanograms per milliliter (ng/mL) and transferrin saturation (TSAT) ≥20% during Screening
Exclusion Criteria:
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Anemia due to a cause other than CKD or participant with active bleeding or recent blood loss
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Red blood cell transfusion within 8 weeks prior to randomization
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Uncontrolled hypertension
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Severe heart failure at Screening (New York Heart Association Class IV)
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Acute coronary syndrome (hospitalization for unstable angina or myocardial infarction), surgical or percutaneous intervention for coronary, cerebrovascular, or peripheral artery disease (aortic or lower extremity), surgical or percutaneous valvular replacement or repair, sustained ventricular tachycardia, hospitalization for heart failure, or stroke within 12 weeks prior to or during Screening
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Hypersensitivity to Darbepoetin or Vadadustat or to any of their excipients
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Research Site | Birmingham | Alabama | United States | 35211 |
2 | Research Site | Huntsville | Alabama | United States | 35805 |
3 | Research Site | Tuscumbia | Alabama | United States | 35674 |
4 | Research Site | Glendale | Arizona | United States | 85306 |
5 | Research Site | Mesa | Arizona | United States | 85210 |
6 | Research Site | Phoenix | Arizona | United States | 85027 |
7 | Research Site | Tucson | Arizona | United States | 85718 |
8 | Research Site | Tucson | Arizona | United States | 85724 |
9 | Research Site | Anaheim | California | United States | 92801 |
10 | Research Site | Bakersfield | California | United States | 93309 |
11 | Research Site #1 | Chula Vista | California | United States | 91910 |
12 | Research Site #2 | Chula Vista | California | United States | 91910 |
13 | Research Site | El Centro | California | United States | 92243 |
14 | Research Site | Fountain Valley | California | United States | 92708 |
15 | Research Site | Glendale | California | United States | 91206 |
16 | Research Site | Granada Hills | California | United States | 91344 |
17 | Research Site | La Mesa | California | United States | 91942 |
18 | Research Site | Laguna Hills | California | United States | 92653 |
19 | Research Site | Long Beach | California | United States | 90807 |
20 | Research Site | Long Beach | California | United States | 92886 |
21 | Research Site | Los Angeles | California | United States | 90048 |
22 | Research Site | Lynwood | California | United States | 90260 |
23 | Research Site #1 | Northridge | California | United States | 91324 |
24 | Research Site #2 | Northridge | California | United States | 91324 |
25 | Research Site | Riverside | California | United States | 92505 |
26 | Research Site | Roseville | California | United States | 95661 |
27 | Research Site | Salinas | California | United States | 93901 |
28 | Research Site | San Diego | California | United States | 92103-6204 |
29 | Research Site #1 | San Dimas | California | United States | 91773 |
30 | Research Site #2 | San Dimas | California | United States | 91773 |
31 | Research Site | Santa Ana | California | United States | 92704 |
32 | Research Site | Santa Monica | California | United States | 90404 |
33 | Research Site | Sherman Oaks | California | United States | 91403 |
34 | Research Site | Thousand Oaks | California | United States | 91360 |
35 | Research Site | Whittier | California | United States | 90603 |
36 | Research Site | Whittier | California | United States | 99999 |
37 | Research Site | Arvada | Colorado | United States | 80002 |
38 | Research Site | Denver | Colorado | United States | 80230 |
39 | Research Site | Westminster | Colorado | United States | 80031 |
40 | Research Site | Stamford | Connecticut | United States | 06902 |
41 | Research Site | Waterbury | Connecticut | United States | 06708 |
42 | Research Site | Bradenton | Florida | United States | 34209 |
43 | Research Site | Brandon | Florida | United States | 33511 |
44 | Research Site | Cooper City | Florida | United States | 33024 |
45 | Research Site #1 | Coral Gables | Florida | United States | 33134 |
46 | Research Site #2 | Coral Gables | Florida | United States | 33134 |
47 | Research Site | Coral Springs | Florida | United States | 33065 |
48 | Research Site | Coral Springs | Florida | United States | 33071 |
49 | Research Site | Doral | Florida | United States | 33166 |
50 | Research Site | Edgewater | Florida | United States | 32132 |
51 | Research Site | Hialeah | Florida | United States | 33010 |
52 | Research Site #1 | Hialeah | Florida | United States | 33012 |
53 | Research Site #2 | Hialeah | Florida | United States | 33012 |
54 | Research Site #3 | Hialeah | Florida | United States | 33012 |
55 | Research Site | Hialeah | Florida | United States | 33018 |
56 | Research Site #1 | Hollywood | Florida | United States | 33024 |
57 | Research Site #2 | Hollywood | Florida | United States | 33024 |
58 | Research Site | Jacksonville | Florida | United States | 32204 |
59 | Research Site #1 | Jacksonville | Florida | United States | 32216 |
60 | Research Site #2 | Jacksonville | Florida | United States | 32216 |
61 | Research Site | Lake Worth | Florida | United States | 33467 |
62 | Research Site | Lauderdale Lakes | Florida | United States | 33313 |
63 | Research Site | Miami Beach | Florida | United States | 33140 |
64 | Research Site | Miami Lakes | Florida | United States | 33014 |
65 | Research Site #1 | Miami Lakes | Florida | United States | 33016 |
66 | Research Site #2 | Miami Lakes | Florida | United States | 33016 |
67 | Research Site | Miami | Florida | United States | 33122 |
68 | Research Site | Miami | Florida | United States | 33125-4141 |
69 | Research Site #1 | Miami | Florida | United States | 33126 |
70 | Research Site #2 | Miami | Florida | United States | 33126 |
71 | Research Site | Miami | Florida | United States | 33133 |
72 | Research Site | Miami | Florida | United States | 33134 |
73 | Research Site | Miami | Florida | United States | 33135 |
74 | Research Site | Miami | Florida | United States | 33143 |
75 | Research Site #1 | Miami | Florida | United States | 33144 |
76 | Research Site #2 | Miami | Florida | United States | 33144 |
77 | Research Site | Miami | Florida | United States | 33145 |
78 | Research Site | Miami | Florida | United States | 33150 |
79 | Research Site | Miami | Florida | United States | 33157 |
80 | Research Site | Miami | Florida | United States | 33165 |
81 | Research Site | Miami | Florida | United States | 33169 |
82 | Research Site | Miami | Florida | United States | 33173 |
83 | Research Site #1 | Miami | Florida | United States | 33175 |
84 | Research Site #2 | Miami | Florida | United States | 33175 |
85 | Research Site | Pembroke Pines | Florida | United States | 33026 |
86 | Research Site | Pompano Beach | Florida | United States | 33060 |
87 | Research Site | Port Charlotte | Florida | United States | 33952 |
88 | Research Site | Tampa | Florida | United States | 33604 |
89 | Research Site | Tampa | Florida | United States | 33612 |
90 | Research Site | Tampa | Florida | United States | 33614 |
91 | Research Site | Atlanta | Georgia | United States | 30338 |
92 | Research Site | Atlanta | Georgia | United States | 30342 |
93 | Research Site | Atlanta | Georgia | United States | 30350 |
94 | Research Site | Augusta | Georgia | United States | 30909 |
95 | Research Site | Columbus | Georgia | United States | 31901 |
96 | Research Site #1 | Columbus | Georgia | United States | 31904 |
97 | Research Site #2 | Columbus | Georgia | United States | 31904 |
98 | Research Site #1 | Lawrenceville | Georgia | United States | 30046 |
99 | Research Site #2 | Lawrenceville | Georgia | United States | 30046 |
100 | Research Site | Macon | Georgia | United States | 31217 |
101 | Research Site | Meridian | Idaho | United States | 83642 |
102 | Research Site | Chicago | Illinois | United States | 60637 |
103 | Research Site | Elk Grove Village | Illinois | United States | 60007 |
104 | Research Site | Evanston | Illinois | United States | 60201 |
105 | Research Site | McHenry | Illinois | United States | 60050 |
106 | Research Site | Peoria | Illinois | United States | 61603 |
107 | Research Site | Anderson | Indiana | United States | 46011 |
108 | Research Site | Fort Wayne | Indiana | United States | 46804 |
109 | Research Site | Jeffersonville | Indiana | United States | 47130 |
110 | Research Site #1 | Merrillville | Indiana | United States | 46410 |
111 | Research Site #2 | Merrillville | Indiana | United States | 46410 |
112 | Research Site | Michigan City | Indiana | United States | 46360 |
113 | Research Site | Muncie | Indiana | United States | 47304 |
114 | Research Site | Monroe | Louisiana | United States | 71201 |
115 | Research Site | New Orleans | Louisiana | United States | 70115 |
116 | Research Site | Shreveport | Louisiana | United States | 71101 |
117 | Research Site | Shreveport | Louisiana | United States | 71103 |
118 | Research Site | Portland | Maine | United States | 04102 |
119 | Research Site | Baltimore | Maryland | United States | 21218 |
120 | Research Site | Greenbelt | Maryland | United States | 20770 |
121 | Research Site | Takoma Park | Maryland | United States | 20912 |
122 | Research Site | Methuen | Massachusetts | United States | 01844 |
123 | Research Site | Plymouth | Massachusetts | United States | 02360 |
124 | Research Site | Springfield | Massachusetts | United States | 01107 |
125 | Research Site | Detroit | Michigan | United States | 48202 |
126 | Research Site | Pontiac | Michigan | United States | 48341 |
127 | Research Site | Port Huron | Michigan | United States | 91344 |
128 | Research Site | Roseville | Michigan | United States | 48066 |
129 | Research Site | Minneapolis | Minnesota | United States | 55404 |
130 | Research Site | Saint Paul | Minnesota | United States | 55102 |
131 | Research Site | Gulfport | Mississippi | United States | 39501 |
132 | Research Site | Columbia | Missouri | United States | 65201 |
133 | Research Site | Kansas City | Missouri | United States | 64111 |
134 | Research Site | Kansas City | Missouri | United States | 64128 |
135 | Research Site | Butte | Montana | United States | 59701 |
136 | Research Site | Lincoln | Nebraska | United States | 68510 |
137 | Research Site | Omaha | Nebraska | United States | 68124 |
138 | Research Site #1 | Las Vegas | Nevada | United States | 89106 |
139 | Research Site #2 | Las Vegas | Nevada | United States | 89106 |
140 | Research Site | Portsmouth | New Hampshire | United States | 03801 |
141 | Research Site | Berlin | New Jersey | United States | 08009 |
142 | Research Site | Voorhees | New Jersey | United States | 08043 |
143 | Research Site | Albuquerque | New Mexico | United States | 87106 |
144 | Research Site | Albuquerque | New Mexico | United States | 87108 |
145 | Research Site | Albuquerque | New Mexico | United States | 87109 |
146 | Research Site | Santa Fe | New Mexico | United States | 87505 |
147 | Research Site | Bronx | New York | United States | 10467 |
148 | Research Site | Flushing | New York | United States | 11355 |
149 | Research Site | Laurelton | New York | United States | 11413 |
150 | Research Site | Mineola | New York | United States | 11501 |
151 | Research Site | New York | New York | United States | 10010 |
152 | Research Site | Asheville | North Carolina | United States | 28801 |
153 | Research Site #1 | Greenville | North Carolina | United States | 27834 |
154 | Research Site #2 | Greenville | North Carolina | United States | 27834 |
155 | Research Site | Jacksonville | North Carolina | United States | 28546 |
156 | Research Site | Kinston | North Carolina | United States | 28504 |
157 | Research Site | Morehead City | North Carolina | United States | 28557 |
158 | Research Site | New Bern | North Carolina | United States | 28560 |
159 | Research Site | Wilmington | North Carolina | United States | 28401 |
160 | Research Site | Winston-Salem | North Carolina | United States | 27103 |
161 | Research Site | Akron | Ohio | United States | 44302 |
162 | Research Site | Columbus | Ohio | United States | 43203 |
163 | Research Site | Marion | Ohio | United States | 43302 |
164 | Research Site | Maumee | Ohio | United States | 43537 |
165 | Research Site | Portland | Oregon | United States | 97216 |
166 | Research Site | Doylestown | Pennsylvania | United States | 18901 |
167 | Research Site | Jersey Shore | Pennsylvania | United States | 17740 |
168 | Research Site | Philadelphia | Pennsylvania | United States | 19140 |
169 | Research Site | East Providence | Rhode Island | United States | 02915 |
170 | Research Site | Providence | Rhode Island | United States | 02908 |
171 | Research Site | Anderson | South Carolina | United States | 29625 |
172 | Research Site | Columbia | South Carolina | United States | 29203 |
173 | Research Site | Orangeburg | South Carolina | United States | 29118 |
174 | Research Site | Sumter | South Carolina | United States | 29150-1900 |
175 | Research Site | West Columbia | South Carolina | United States | 29169 |
176 | Research Site | Chattanooga | Tennessee | United States | 37408 |
177 | Research Site | Knoxville | Tennessee | United States | 37923 |
178 | Research Site | Memphis | Tennessee | United States | 38104 |
179 | Research Site | Nashville | Tennessee | United States | 37205 |
180 | Research Site | Arlington | Texas | United States | 76015 |
181 | Research Site | Dallas | Texas | United States | 75220 |
182 | Research Site | Dallas | Texas | United States | 75390 |
183 | Research Site | DeSoto | Texas | United States | 75115 |
184 | Research Site | El Paso | Texas | United States | 79935 |
185 | Research Site | Fort Worth | Texas | United States | 76104 |
186 | Research Site | Gonzales | Texas | United States | 78629 |
187 | Research Site | Greenville | Texas | United States | 75401 |
188 | Research Site | Greenville | Texas | United States | 75402 |
189 | Research Site | Houston | Texas | United States | 33143 |
190 | Research Site #1 | Houston | Texas | United States | 77004 |
191 | Research Site #2 | Houston | Texas | United States | 77004 |
192 | Research Site | Houston | Texas | United States | 77054 |
193 | Research Site | Lewisville | Texas | United States | 75057 |
194 | Research Site #1 | McAllen | Texas | United States | 78503 |
195 | Research Site #2 | McAllen | Texas | United States | 78503 |
196 | Research Site | McKinney | Texas | United States | 75069 |
197 | Research Site | McKinney | Texas | United States | 75071 |
198 | Research Site | Plano | Texas | United States | 75024-5327 |
199 | Research Site | San Antonio | Texas | United States | 78207 |
200 | Research Site | San Antonio | Texas | United States | 78212-4740 |
201 | Research Site | San Antonio | Texas | United States | 78224 |
202 | Research Site | San Antonio | Texas | United States | 78240-1501 |
203 | Research Site | Sherman | Texas | United States | 75090 |
204 | Research Site | Victoria | Texas | United States | 77901 |
205 | Research Site | Clinton | Utah | United States | 84015 |
206 | Research Site | Saint George | Utah | United States | 84790 |
207 | Research Site | Salt Lake City | Utah | United States | 84115 |
208 | Research Site | Burlington | Vermont | United States | 05401 |
209 | Research Site | Alexandria | Virginia | United States | 22304 |
210 | Research Site | Arlington | Virginia | United States | 22207 |
211 | Research Site | Danville | Virginia | United States | 24541 |
212 | Research Site | Hampton | Virginia | United States | 23666 |
213 | Research Site | Lansdowne Town Center | Virginia | United States | 20176 |
214 | Research Site | Norfolk | Virginia | United States | 23507 |
215 | Research Site | Salem | Virginia | United States | 24153 |
216 | Research Site | Woodbridge | Virginia | United States | 22191 |
217 | Research Site | Tacoma | Washington | United States | 98405 |
218 | Research Site | Wenatchee | Washington | United States | 98801 |
219 | Research Site | Madison | Wisconsin | United States | 53705 |
220 | Research Site | Bahia Blanca | Buenos Aires | Argentina | B8001HXM |
221 | Research Site | Junin | Buenos Aires | Argentina | 6000 |
222 | Research Site | Junin | Buenos Aires | Argentina | B6000BHA |
223 | Research Site | Mar del Plata | Buenos Aires | Argentina | B7600FYK |
224 | Research Site | Mar del Plata | Buenos Aires | Argentina | B7600FZ |
225 | Research Site | Mar del Plata | Buenos Aires | Argentina | B7602DCK |
226 | Research Site | Pergamino | Buenos Aires | Argentina | B2700CPM |
227 | Research Site | Ramos Mejia | Buenos Aires | Argentina | B1704ETD |
228 | Research Site | San Miguel | Buenos Aires | Argentina | B1663CNJ |
229 | Research Site | San Nicolas | Buenos Aires | Argentina | B2900DMH |
230 | Research Site | Sarandi | Buenos Aires | Argentina | B1872EEA |
231 | Research Site | Temperley | Buenos Aires | Argentina | 1834 |
232 | Research Site | Godoy Cruz | Mendoza | Argentina | 5501 |
233 | Research Site | Rosario | Santa Fe | Argentina | S2000DIF |
234 | Research Site | Rosario | Santa Fe | Argentina | S2000DNM |
235 | Research Site | San Miguel de Tucuman | Tucuman | Argentina | 4000 |
236 | Research Site | San Miguel de Tucuman | Tucuman | Argentina | T4000AXL |
237 | Research Site | San Miguel de Tucuman | Tucuman | Argentina | T4000ICL |
238 | Research Site | San Miguel de Tucuman | Tucuman | Argentina | T4000 |
239 | Research Site | Ciudad Autonoma Buenos Aires | Argentina | C1093AAS | |
240 | Research Site | Ciudad Autonoma Buenos Aires | Argentina | C1430CKE | |
241 | Research Site | Cordoba | Argentina | 5000 | |
242 | Research Site | Cordoba | Argentina | X5000AAW | |
243 | Research Site | Cordoba | Argentina | X5000EVQ | |
244 | Research Site | Cordoba | Argentina | X5020AAA | |
245 | Research Site | Corrientes | Argentina | 3400 | |
246 | Research Site | Salta | Argentina | 4406 | |
247 | Research Site | San Luis | Argentina | 5700 | |
248 | Research Site | Camperdown | New South Wales | Australia | 2050 |
249 | Research Site | Liverpool | New South Wales | Australia | 2170 |
250 | Research Site | Westmead | New South Wales | Australia | 2145 |
251 | Research Site | Cairns | Queensland | Australia | 4870 |
252 | Research Site | Gold Coast | Queensland | Australia | 9726 |
253 | Research Site | Adelaide | South Australia | Australia | 5000 |
254 | Research Site | Launceston | Tasmania | Australia | 7250 |
255 | Research Site | Bentleigh East | Victoria | Australia | 3165 |
256 | Research Site | Box Hill | Victoria | Australia | 3128 |
257 | Research Site | Fitzroy | Victoria | Australia | 3065 |
258 | Research Site | Nedlands | Western Australia | Australia | 6009 |
259 | Research Site | Perth | Western Australia | Australia | 6000 |
260 | Research Site | St. Pölten | Austria | 3100 | |
261 | Research Site | Wien | Austria | 1030 | |
262 | Research Site | Wien | Austria | 1220 | |
263 | Research Site | Feira de Santana | Bahia | Brazil | 44001-584 |
264 | Research Site | Itabuna | Bahia | Brazil | 45600-625 |
265 | Research Site | Salvador | Bahia | Brazil | 40451-065 |
266 | Research Site | Fortaleza | Ceará | Brazil | 60115-282 |
267 | Research Site | Fortaleza | Ceará | Brazil | 60430-370 |
268 | Research Site | Vitória | Espírito Santo | Brazil | 29055-450 |
269 | Research Site | Belo Horizonte | Minas Gerais | Brazil | 30150-320 |
270 | Research Site | Juiz de Fora | Minas Gerais | Brazil | 36036-330 |
271 | Research Site | Curitiba | Paraná | Brazil | 80230-130 |
272 | Research Site #1 | Curitiba | Paraná | Brazil | 80810-040 |
273 | Research Site #2 | Curitiba | Paraná | Brazil | 80810-040 |
274 | Research Site | Maringá | Paraná | Brazil | 87060-040 |
275 | Research Site | Rio de Janeiro | Rio Do Janeiro | Brazil | 20551-030 |
276 | Research Site | Caxias do Sul | Rio Grande Do Sul | Brazil | 95010-005 |
277 | Research Site | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-074 |
278 | Research Site | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
279 | Research Site | Porto Alegre | Rio Grande Do Sul | Brazil | 90160-093 |
280 | Research Site | Porto Alegre | Rio Grande Do Sul | Brazil | 90610-000 |
281 | Research Site | Criciúma | Santa Catarina | Brazil | 88801-250 |
282 | Research Site | Joinville | Santa Catarina | Brazil | 89202-050 |
283 | Research Site | Botucatu | Sao Paulo | Brazil | 18618-970 |
284 | Research Site | Campinas | Sao Paulo | Brazil | 13087-567 |
285 | Research Site | Santo André | Sao Paulo | Brazil | 09080-110 |
286 | Research Site | Santo André | Sao Paulo | Brazil | 09090-790 |
287 | Research Site | São Bernardo do Campo | Sao Paulo | Brazil | 09715-090 |
288 | Research Site | São Paulo | Sao Paulo | Brazil | 01141-020 |
289 | Research Site | São Paulo | Sao Paulo | Brazil | 01406-200 |
290 | Research Site | São Paulo | Sao Paulo | Brazil | 04025-011 |
291 | Research Site | São Paulo | Sao Paulo | Brazil | 05403-000 |
292 | Research Site | Byala | Bulgaria | 7100 | |
293 | Research Site | Cherven bryag | Bulgaria | 5980 | |
294 | Research Site | Lom | Bulgaria | 3600 | |
295 | Research Site | Silistra | Bulgaria | 7500 | |
296 | Research Site | Sliven | Bulgaria | 8800 | |
297 | Research Site | Smolyan | Bulgaria | 4700 | |
298 | Research Site | Sofia | Bulgaria | 1233 | |
299 | Research Site | Sofia | Bulgaria | 1407 | |
300 | Research Site #1 | Sofia | Bulgaria | 1431 | |
301 | Research Site #2 | Sofia | Bulgaria | 1431 | |
302 | Research Site | Sofia | Bulgaria | 1606 | |
303 | Research Site | Sofia | Bulgaria | 1784 | |
304 | Research Site | Stara Zagora | Bulgaria | 6000 | |
305 | Research Site | Varna | Bulgaria | 9000 | |
306 | Research Site | Varna | Bulgaria | 9002 | |
307 | Research Site | Veliko Tarnovo | Bulgaria | 5000 | |
308 | Research Site | Vratsa | Bulgaria | 3000 | |
309 | Research Site | Scarborough | Ontario | Canada | M1H 3G4 |
310 | Research Site | Concepción | Chile | 4030000 | |
311 | Research Site | Puerto Varas | Chile | 5550170 | |
312 | Research Site | Santiago | Chile | 8431657 | |
313 | Research Site | Temuco | Chile | 4780000 | |
314 | Research Site | Barranquilla | Colombia | 080020 | |
315 | Research Site | Bogota | Colombia | 110221 | |
316 | Research Site | Espinal | Colombia | 00000 | |
317 | Research Site | Manizales | Colombia | 170004 | |
318 | Research Site #1 | Medellin | Colombia | 050021 | |
319 | Research Site #2 | Medellin | Colombia | 050021 | |
320 | Research Site | Medellín | Colombia | 500515 | |
321 | Research Site | Ceske Budejovice | Czechia | 370 01 | |
322 | Research Site | Hradec Kralove | Czechia | 50333 | |
323 | Research Site | Praha 2 | Czechia | 128 08 | |
324 | Research Site | Praha 4 | Czechia | 140 21 | |
325 | Research Site | Lille | Alpes De Haute Provence | France | 59000 |
326 | Research Site | Saint-Priest-En-Jarez | Loire | France | 42055 |
327 | Research Site | Reims Cedex | Marne | France | 51090 |
328 | Research Site | Pontoise | Val d'Oise | France | 95300 |
329 | Research Site | Créteil Cedex | Val De Marne | France | 94010 |
330 | Research Site | Paris | France | 75015 | |
331 | Research Site | Paris | France | 75020 | |
332 | Research Site | Villingen-Schwenningen | Baden Wuerttemberg | Germany | 78052 |
333 | Research Site | Rostock | Mecklenburg Vorpommern | Germany | 18057 |
334 | Research Site | Duesseldorf | Nordrhein Westfalen | Germany | 40210 |
335 | Research Site | Berlin | Germany | 10117 | |
336 | Research Site | Berlin | Germany | 12627 | |
337 | Research Site | Hamburg | Germany | 22297 | |
338 | Research Site #1 | Baja | Hungary | 6500 | |
339 | Research Site #2 | Baja | Hungary | 6500 | |
340 | Research Site | Balatonfured | Hungary | 8230 | |
341 | Research Site | Budapest | Hungary | 1076 | |
342 | Research Site | Budapest | Hungary | 1145 | |
343 | Research Site | Debrecen | Hungary | 4032 | |
344 | Research Site | Esztergom | Hungary | 2500 | |
345 | Research Site | Hodmezovasarhely | Hungary | 6800 | |
346 | Research Site | Kalocsa | Hungary | 6300 | |
347 | Research Site | Kaposvar | Hungary | 7400 | |
348 | Research Site | Kecskemet | Hungary | 6000 | |
349 | Research Site | Kistarcsa | Hungary | 2143 | |
350 | Research Site | Pecs | Hungary | 7623 | |
351 | Research Site | Szeged | Hungary | 6720 | |
352 | Research Site | Szigetvar | Hungary | 7900 | |
353 | Research Site | Ashkelon | Israel | 78278 | |
354 | Research Site | Haifa | Israel | 3109601 | |
355 | Research Site | Nahariya | Israel | 2210001 | |
356 | Research Site | Ramat Gan | Israel | 52363 | |
357 | Research Site | Rishon Lezion | Israel | 75141 | |
358 | Research Site | Piedimonte Matese | Caserta | Italy | 81016 |
359 | Research Site | San Giovanni Rotondo | Foggia | Italy | 71013 |
360 | Research Site | Bari | Italy | 70124 | |
361 | Research Site | Lecco | Italy | 23900 | |
362 | Research Site | Milano | Italy | 20142 | |
363 | Research Site | Milano | Italy | 20162 | |
364 | Research Site #1 | Napoli | Italy | 80138 | |
365 | Research Site #2 | Napoli | Italy | 80138 | |
366 | Research Site | Parma | Italy | 43100 | |
367 | Research Site | Pavia | Italy | 27100 | |
368 | Research Site | Roma | Italy | 00168 | |
369 | Research Site | Siena | Italy | 53100 | |
370 | Research Site | Bucheon-si | Gyeonggi-do | Korea, Republic of | 14647 |
371 | Research Site | Goyang-si | Gyeonggi-do | Korea, Republic of | 10380 |
372 | Research Site | Guri-si | Gyeonggi-do | Korea, Republic of | 11923 |
373 | Research Site | Seongnam-si | Gyeonggi-do | Korea, Republic of | 13620 |
374 | Research Site | Busan | Korea, Republic of | 47392 | |
375 | Research Site | Busan | Korea, Republic of | 49201 | |
376 | Research Site | Daegu | Korea, Republic of | 41944 | |
377 | Research Site | Seoul | Korea, Republic of | 02841 | |
378 | Research Site | Seoul | Korea, Republic of | 03080 | |
379 | Research Site | Seoul | Korea, Republic of | 06591 | |
380 | Research Site | Seoul | Korea, Republic of | 07345 | |
381 | Research Site | Seoul | Korea, Republic of | 135-710 | |
382 | Research Site | Alor Setar | Kedah | Malaysia | 05460 |
383 | Research Site | Kuala Lumpur | Malaysia | 56000 | |
384 | Research Site | Kuala Lumpur | Malaysia | 59100 | |
385 | Research Site | Pulau Pinang | Malaysia | 10990 | |
386 | Research Site | Torreon | Coahuila | Mexico | 27000 |
387 | Research Site | Mexico | Distrito Federal | Mexico | 06100 |
388 | Research Site | Mexico | Distrito Federal | Mexico | 06700 |
389 | Research Site | Acapulco de Juarez | Guerrero | Mexico | 39670 |
390 | Research Site #1 | Pachuca | Hidalgo | Mexico | 42070 |
391 | Research Site #2 | Pachuca | Hidalgo | Mexico | 42070 |
392 | Research Site | Guadalajara | Jalisco | Mexico | 44130 |
393 | Research Site | Zapopan | Jalisco | Mexico | 45030 |
394 | Research Site | Zapopan | Jalisco | Mexico | 45116 |
395 | Research Site | Zapopan | Jalisco | Mexico | 45200 |
396 | Research Site | Morelia | Michoacán | Mexico | 58260 |
397 | Research Site | Monterrey | Nuevo León | Mexico | 64620 |
398 | Research Site | Monterrey | Nuevo León | Mexico | 64710 |
399 | Research Site | San Juan del Rio | Queretaro | Mexico | 76800 |
400 | Research Site | Culiacan | Sinaloa | Mexico | 80200 |
401 | Research Site | Culiacan | Sinaloa | Mexico | 80230 |
402 | Research Site | Culiacán | Sinaloa | Mexico | 80030 |
403 | Research Site | Mazatlan | Sinaloa | Mexico | 82110 |
404 | Research Site | Chihuahua | Mexico | 31203 | |
405 | Research Site | Chihuahua | Mexico | 31217 | |
406 | Research Site | Durango | Mexico | 34000 | |
407 | Research Site | Veracruz | Mexico | 91900 | |
408 | Research Site | Hamilton | New Zealand | 3200 | |
409 | Research Site | New Plymouth | New Zealand | 4342 | |
410 | Research Site | Nowa Sol | Poland | 67-100 | |
411 | Research Site | Caguas | Puerto Rico | 00725 | |
412 | Research Site | Bucuresti | Romania | 010719 | |
413 | Research Site | Bucuresti | Romania | 011794 | |
414 | Research Site #1 | Bucuresti | Romania | 022328 | |
415 | Research Site #2 | Bucuresti | Romania | 022328 | |
416 | Research Site | Bucuresti | Romania | 042122 | |
417 | Research Site | Oradea | Romania | 410469 | |
418 | Research Site | Timisoara | Romania | 300182 | |
419 | Research Site | Kazan | Russian Federation | 420012 | |
420 | Research Site | Kemerovo | Russian Federation | 650066 | |
421 | Research Site | Krasnoyarsk | Russian Federation | 660062 | |
422 | Research Site | Nizhniy Novgorod | Russian Federation | 603076 | |
423 | Research Site | Novosibirsk | Russian Federation | 630054 | |
424 | Research Site | Novosibirsk | Russian Federation | 630091 | |
425 | Research Site | Petrozavodsk | Russian Federation | 185019 | |
426 | Research Site | Pushkin | Russian Federation | 196603 | |
427 | Research Site | Saint-Petersburg | Russian Federation | 195271 | |
428 | Research Site | Saint-Petersburg | Russian Federation | 197022 | |
429 | Research Site | Yaroslavl | Russian Federation | 150062 | |
430 | Research Site #1 | Belgrade | Serbia | 11000 | |
431 | Research Site #2 | Belgrade | Serbia | 11000 | |
432 | Research Site #3 | Belgrade | Serbia | 11000 | |
433 | Research Site | Kragujevac | Serbia | 34000 | |
434 | Research Site | Lazarevac | Serbia | 11000 | |
435 | Research Site | Nis | Serbia | 18000 | |
436 | Research Site | Zajecar | Serbia | 19000 | |
437 | Research Site | Bardejov | Slovakia | 08501 | |
438 | Research Site | Bratislava | Slovakia | 83103 | |
439 | Research Site | Galanta | Slovakia | 924 22 | |
440 | Research Site | Svidnik | Slovakia | 08901 | |
441 | Research Site | Trstena | Slovakia | 02801 | |
442 | Research Site | Bloemfontein | Free State | South Africa | 9301 |
443 | Research Site | Brandfort | Free State | South Africa | 9400 |
444 | Research Site | Pretoria | Gauteng | South Africa | 0002 |
445 | Research Site | Pretoria | Gauteng | South Africa | 1692 |
446 | Research Site | Vereeniging | Gauteng | South Africa | 1935 |
447 | Research Site #1 | Durban | KwaZulu-Natal | South Africa | 4001 |
448 | Research Site #2 | Durban | KwaZulu-Natal | South Africa | 4001 |
449 | Research Site | Durban | KwaZulu-Natal | South Africa | 4092 |
450 | Research Site | Durban | KwaZulu-Natal | South Africa | 4320 |
451 | Research Site | Tongaat | KwaZulu-Natal | South Africa | 4399 |
452 | Research Site | Worcester | Western Cape | South Africa | 6850 |
453 | Research Site | Elche | Alicante | Spain | 03293 |
454 | Research Site | Torrevieja | Alicante | Spain | 03186 |
455 | Research Site | Palma de Mallorca | Baleares | Spain | 07120 |
456 | Research Site | L'Hospitalet de Llobregat | Barcelona | Spain | 08907 |
457 | Research Site | Malaga | Málaga | Spain | 29010 |
458 | Research Site | Almeria | Spain | 04007 | |
459 | Research Site | Almeria | Spain | 04009 | |
460 | Research Site | Badajoz | Spain | 06006 | |
461 | Research Site | Barcelona | Spain | 08003 | |
462 | Research Site | Barcelona | Spain | 08025 | |
463 | Research Site | Barcelona | Spain | 08035 | |
464 | Research Site | Madrid | Spain | 28007 | |
465 | Research Site | Madrid | Spain | 28040 | |
466 | Research Site | Madrid | Spain | 28041 | |
467 | Research Site | Pamplona | Spain | 31001 | |
468 | Research Site | Sevilla | Spain | 41013 | |
469 | Research Site | Sevilla | Spain | 41071 | |
470 | Research Site | Valencia | Spain | 46014 | |
471 | Research Site | Valencia | Spain | 46026 | |
472 | Research Site | Ankara | Turkey | 06100 | |
473 | Research Site | Erciyes | Turkey | 38039 | |
474 | Research Site | Istanbul | Turkey | 34098 | |
475 | Research Site | Istanbul | Turkey | 34722 | |
476 | Research Site | Kocaeli | Turkey | 41380 | |
477 | Research Site | Dnipro | Ukraine | 49005 | |
478 | Research Site | Ivano-Frankivsk | Ukraine | 76008 | |
479 | Research Site | Ivano-Frankivsk | Ukraine | 76018 | |
480 | Research Site | Kharkiv | Ukraine | 61037 | |
481 | Research Site | Kharkiv | Ukraine | 61039 | |
482 | Research Site | Kharkiv | Ukraine | 61103 | |
483 | Research Site | Kharkiv | Ukraine | 61157 | |
484 | Research Site | Kropyvnytskyi | Ukraine | 25006 | |
485 | Research Site | Kyiv | Ukraine | 02125 | |
486 | Research Site | Kyiv | Ukraine | 04050 | |
487 | Research Site | Lutsk | Ukraine | 43005 | |
488 | Research Site | Lviv | Ukraine | 79013 | |
489 | Research Site | Mykolaiv | Ukraine | 54058 | |
490 | Research Site | Odesa | Ukraine | 65025 | |
491 | Research Site | Vinnytsia | Ukraine | 21001 | |
492 | Research Site | Vinnytsia | Ukraine | 21005 | |
493 | Research Site | Vinnytsia | Ukraine | 21018 | |
494 | Research Site | Zaporizhzhia | Ukraine | 69118 | |
495 | Research Site | Exeter | Devon | United Kingdom | EX2 5DW |
496 | Research Site | London | Greater London | United Kingdom | E1 1BB |
497 | Research Site | London | Greater London | United Kingdom | SE5 9RS |
498 | Research Site | Salford | Greater Manchester | United Kingdom | M6 8HD |
499 | Research Site | Stevenage | Hertfordshire | United Kingdom | SG1 4AB |
500 | Research Site | Leicester | Leicestershire | United Kingdom | LE5 4PW |
501 | Research Site | King's Lynn | Norfolk | United Kingdom | PE30 4ET |
502 | Research Site | Doncaster | South Yorkshire | United Kingdom | DN2 5LT |
503 | Research Site | Swansea | United Kingdom | SA6 6NL |
Sponsors and Collaborators
- Akebia Therapeutics
Investigators
- Study Director: Chief Medical Officer, Akebia Therapeutics Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.- AKB-6548-CI-0015
- 2015-004774-14
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | A total of 2961 participants were screened for entry into the study. Of these, 1725 participants were enrolled and randomized into the study. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Period Title: Overall Study | ||
STARTED | 862 | 863 |
COMPLETED | 704 | 711 |
NOT COMPLETED | 158 | 152 |
Baseline Characteristics
Arm/Group Title | Vadadustat | Darbepoetin Alfa | Total |
---|---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. | Total of all reporting groups |
Overall Participants | 862 | 863 | 1725 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
67.3
(13.14)
|
66.5
(13.52)
|
66.9
(13.33)
|
Sex: Female, Male (Count of Participants) | |||
Female |
468
54.3%
|
488
56.5%
|
956
55.4%
|
Male |
394
45.7%
|
375
43.5%
|
769
44.6%
|
Race/Ethnicity, Customized (Count of Participants) | |||
American Indian or Alaska Native |
32
3.7%
|
26
3%
|
58
3.4%
|
Asian |
62
7.2%
|
55
6.4%
|
117
6.8%
|
Black or African American |
93
10.8%
|
131
15.2%
|
224
13%
|
Native Hawaiian or Other Pacific Islander |
3
0.3%
|
0
0%
|
3
0.2%
|
White |
631
73.2%
|
603
69.9%
|
1234
71.5%
|
Not Reported |
15
1.7%
|
13
1.5%
|
28
1.6%
|
Reported as Other |
25
2.9%
|
32
3.7%
|
57
3.3%
|
Multiple |
1
0.1%
|
3
0.3%
|
4
0.2%
|
Average hemoglobin (Grams per deciliter (g/dL)) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Grams per deciliter (g/dL)] |
10.423
(0.8871)
|
10.390
(0.9430)
|
10.406
(0.9154)
|
Mean estimated glomerular filtration rate (mL/min/1.73m^2) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [mL/min/1.73m^2] |
22.6
(11.64)
|
22.8
(12.04)
|
22.7
(11.84)
|
Number of Participants with History of Diabetes (Count of Participants) | |||
Count of Participants [Participants] |
444
51.5%
|
432
50.1%
|
876
50.8%
|
Number of Participants with NYHA Functional Classification of Heart Failure (Count of Participants) | |||
NYHA Class 0 |
610
70.8%
|
595
68.9%
|
1205
69.9%
|
NYHA Class I |
108
12.5%
|
108
12.5%
|
216
12.5%
|
NYHA Class II |
113
13.1%
|
122
14.1%
|
235
13.6%
|
NYHA Class III |
29
3.4%
|
36
4.2%
|
65
3.8%
|
NYHA Class IV |
0
0%
|
0
0%
|
0
0%
|
NYHA Class Missing |
2
0.2%
|
2
0.2%
|
4
0.2%
|
Number of Participants with Any History of Heart Failure (Count of Participants) | |||
Yes |
44
5.1%
|
52
6%
|
96
5.6%
|
No |
613
71.1%
|
595
68.9%
|
1208
70%
|
Missing |
205
23.8%
|
216
25%
|
421
24.4%
|
Outcome Measures
Title | Change From Baseline in Hemoglobin (Hb) to the Average Over the Primary Efficacy Period (Weeks 24 to 36) |
---|---|
Description | The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Primary Efficacy Period was calculated as the average Hb value over Weeks 24 to 36. Analysis was conducted using an analysis of covariance (ANCOVA) model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (United States [US] versus European Union [EU] versus Rest of World [ROW]), and New York Heart Association congestive heart failure (NYHA CHF) class (Class 0 [no CHF] or I versus II or III) as covariates. |
Time Frame | Baseline; Weeks 24 to 36 |
Outcome Measure Data
Analysis Population Description |
---|
Randomized Population: All participants randomized. Analyses of this population were based on the randomized treatment. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Measure Participants | 862 | 863 |
Least Squares Mean (Standard Error) [Grams per deciliter (g/dL)] |
0.41
(0.036)
|
0.42
(0.037)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | Treatment comparison: Vadadustat minus Darbepoetin Alfa | |
Type of Statistical Test | Non-Inferiority | |
Comments | Establishment of non-inferiority was based on a margin of -0.75 g/dL applied to the difference in mean change of hemoglobin: Vadadustat minus Darbepoetin alfa | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Least squares mean difference |
Estimated Value | -0.01 | |
Confidence Interval |
(2-Sided) 95% -0.09 to 0.07 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.042 |
|
Estimation Comments |
Title | Median Time to First Major Adverse Cardiovascular Event (MACE) |
---|---|
Description | MACE was defined as all-cause mortality, non-fatal myocardial infarction (MI), or non-fatal stroke. The primary safety outcome was positively adjudicated first MACE, which was defined as any death, Endpoint Adjudication Committee (EAC)-confirmed non-fatal MI, or EAC-confirmed non-fatal stroke occurring between the first dose date and each participant's last participation date. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
Time Frame | Up to Week 208 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population (PRO2TECT): All participants from the PRO2TECT (Non-dialysis-dependent chronic kidney disease [NDD-CKD]) population who received 1 or more doses of study drug. Only those participants with MACE events were analyzed for this outcome measure. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Measure Participants | 168 | 152 |
Median (Inter-Quartile Range) [Weeks] |
53.21
|
58.00
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | Statistical analysis from study AKB-6548-CI-0015 has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per Food and Drug Administration [FDA]) and 1.3 (per European Medicines Agency [EMA]). | |
Statistical Test of Hypothesis | p-Value | =0.2015 |
Comments | ||
Method | Log Rank | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.16 | |
Confidence Interval |
(2-Sided) 95% 0.930 to 1.446 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first MACE for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 382 and 344 respectively; median time to first event (Q1, Q3) = 50.07 (23.00, 82.86) weeks versus 51.93 (27.79, 91.00) weeks, respectively. Statistical analysis from the pooled data has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.0725 |
Comments | ||
Method | Log Rank | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.17 | |
Confidence Interval |
(2-Sided) 95% 1.012 to 1.355 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline in Hb to the Average Over the Secondary Efficacy Period (Weeks 40 to 52) |
---|---|
Description | The Baseline average was calculated as the average of the Hb values obtained at the screening visit closest to the date of randomization and the randomization visit. The average for the Secondary Efficacy Period was calculated as the average Hb value over Weeks 40 to 52. Analysis was conducted using an ANCOVA model with multiple imputation for missing data with Baseline hemoglobin concentration (<10.0 versus ≥10.0 g/dL), geographic region (US versus EU versus ROW), and NYHA CHF class (Class 0 [no CHF] or I versus II or III) as covariates. |
Time Frame | Baseline; Weeks 40 to 52 |
Outcome Measure Data
Analysis Population Description |
---|
Randomized Population. Analyses of this population were based on the randomized treatment. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Measure Participants | 862 | 863 |
Least Squares Mean (Standard Error) [g/dL] |
0.43
(0.044)
|
0.44
(0.044)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | Treatment comparison: Vadadustat minus Darbepoetin Alfa | |
Type of Statistical Test | Non-Inferiority | |
Comments | Establishment of non-inferiority was based on a margin of -0.75 g/dL applied to the difference in mean change: Vadadustat minus Darbepoetin alfa. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Least squares mean difference |
Estimated Value | -0.00 | |
Confidence Interval |
(2-Sided) 95% -0.10 to 0.09 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.05 |
|
Estimation Comments |
Title | Median Time to First MACE Plus Hospitalization for Heart Failure or Thromboembolic Event Excluding Vascular Access Thrombosis |
---|---|
Description | MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Hospitalization for EAC adjudicated heart failure included presentation of participants to an acute care facility requiring an overnight hospitalization (change in calendar day) with an exacerbation of heart failure requiring treatment. EAC confirmed thromboembolic events for this secondary outcome measure included arterial thrombosis, deep vein thrombosis, and pulmonary embolism. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
Time Frame | Up to Week 208 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population (PRO2TECT). Only those participants with MACE plus hospitalization for heart failure or thromboembolic event excluding vascular access thrombosis were analyzed for this outcome measure. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Measure Participants | 197 | 195 |
Median (Inter-Quartile Range) [Weeks] |
48.29
|
49.29
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | Statistical analysis from study AKB-6548-CI-0015 has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.7770 |
Comments | ||
Method | Log Rank | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.04 | |
Confidence Interval |
(2-Sided) 95% 0.851 to 1.268 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first MACE plus hospitalization for heart failure or thromboembolic events excluding vascular access thrombosis for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 451 and 424 respectively; median time to first event (Q1, Q3) = 42.86 (19.71, 73.43) weeks versus 43.86 (21.36, 80.43) weeks, respectively. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.2305 |
Comments | ||
Method | Log Rank | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.11 | |
Confidence Interval |
(2-Sided) 95% 0.972 to 1.267 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Time to First Cardiovascular MACE |
---|---|
Description | MACE was defined as all-cause mortality, non-fatal MI, or non-fatal stroke. Cardiovascular MACE analysis differed from the primary MACE endpoint as it included only deaths adjudicated by the EAC as cardiovascular deaths (i.e, only EAC-confirmed cardiovascular deaths) in addition to first events of non-fatal MI or non-fatal stroke. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
Time Frame | Up to Week 208 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population (PRO2TECT). Only those participants with cardiovascular MACE events were analyzed for this outcome measure. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Measure Participants | 89 | 83 |
Median (Inter-Quartile Range) [Weeks] |
45.57
|
50.29
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | Statistical analysis from study AKB-6548-CI-0015 has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.5509 |
Comments | ||
Method | Gray's Test | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.11 | |
Confidence Interval |
(2-Sided) 95% 0.817 to 1.501 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first cardiovascular MACE for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 198 and 178 respectively; median time to first event (Q1, Q3) = 45.57 (21.71, 73.29) weeks versus 47.36 (20.00, 88.43) weeks, respectively. Statistical analysis from the pooled data has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.2531 |
Comments | ||
Method | Gray's Test | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.16 | |
Confidence Interval |
(2-Sided) 95% 0.947 to 1.420 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Time to First Cardiovascular Death |
---|---|
Description | Cardiovascular death included EAC adjudicated fatal MI, pump failure, sudden death, presumed sudden death, fatal stroke, fatal pulmonary embolism, cardiovascular procedure-related death, other cardiovascular death, and presumed cardiovascular death. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
Time Frame | Up to Week 208 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population (PRO2TECT). Only those participants with cardiovascular death were analyzed for this outcome measure. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Measure Participants | 56 | 66 |
Median (Inter-Quartile Range) [Weeks] |
48.29
|
54.21
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | Statistical analysis from study AKB-6548-CI-0015 has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.4184 |
Comments | ||
Method | Gray's test | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.88 | |
Confidence Interval |
(2-Sided) 95% 0.610 to 1.258 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first cardiovascular death for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 127 and 131 respectively; median time to first event (Q1, Q3) = 48.29 (28.86, 76.14) weeks versus 48.43 (21.29, 92.29) weeks, respectively. Statistical analysis from the pooled data has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.8613 |
Comments | ||
Method | Gray's test | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.01 | |
Confidence Interval |
(2-Sided) 95% 0.792 to 1.293 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Time to First All-cause Mortality |
---|---|
Description | Only events that were positively adjudicated and confirmed by the EAC were included in the MACE analyses. PROTECT MACE results and analysis, by design, was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Results and statistical analysis from study AKB-6548-CI-0015 has been reported in below table and under section "Statistical Analysis 1". Results and statistical analysis of the pooled data from studies AKB-6548-CI-0014 and AKB-6548-CI-0015 has been reported under section "Statistical Analysis 2" of this outcome measure. |
Time Frame | Up to Week 208 |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population (PRO2TECT). Only those participants with all-cause mortality were analyzed for this outcome measure. |
Arm/Group Title | Vadadustat | Darbepoetin Alfa |
---|---|---|
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. |
Measure Participants | 139 | 139 |
Median (Inter-Quartile Range) [Weeks] |
57.71
|
62.14
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | Statistical analysis from study AKB-6548-CI-0015 has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.8041 |
Comments | ||
Method | Log Rank | |
Comments | Based on non-parametric analysis. | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.04 | |
Confidence Interval |
(2-Sided) 95% 0.820 to 1.315 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vadadustat, Darbepoetin Alfa |
---|---|---|
Comments | MACE analysis was performed on pooled data from studies AKB-6548-CI-0014 (NCT02648347) and AKB-6548-CI-0015 (NCT02680574). Time to first all-cause mortality for the Vadadustat and Darbepoetin alfa treatment groups was as follows: participants with events = 319 and 307 respectively; median time to first event (Q1, Q3) = 52.14 (28.71, 84.71) weeks versus 53.00 (30.71, 94.14) weeks, respectively. Statistical analysis from the pooled data has been reported in this section. | |
Type of Statistical Test | Non-Inferiority | |
Comments | The prespecified non-inferiority margin was 1.25 (per FDA) and 1.3 (per EMA). | |
Statistical Test of Hypothesis | p-Value | =0.4577 |
Comments | ||
Method | Log Rank | |
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.09 | |
Confidence Interval |
(2-Sided) 95% 0.930 to 1.274 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) |
---|---|
Description | |
Time Frame | Weeks 24 to 36 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Proportion of Time With Hb Values Within the Target Range During the Primary Evaluation Period (Weeks 24 to 36) |
---|---|
Description | |
Time Frame | Weeks 24 to 36 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Proportion of Time With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) |
---|---|
Description | |
Time Frame | Weeks 40 to 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Proportion of Participants With Hb Values Within the Target Range During the Secondary Evaluation Period (Weeks 40 to 52) |
---|---|
Description | |
Time Frame | Weeks 40 to 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Proportion of Participants With an Hb Increase of >1.0 g/dL From Baseline Visit |
---|---|
Description | |
Time Frame | Baseline; up to Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Time to Achieve Hb Increase of >1.0 g/dL From Baseline Visit |
---|---|
Description | |
Time Frame | Baseline; up to Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Mean Change in Hb Between Baseline (Mean Pretreatment Hb) and the Primary Evaluation Period (Mean Hb From Weeks 24 to 36) Stratified by Pre-baseline Erythropoiesis-stimulating Agent (ESA) Exposure |
---|---|
Description | |
Time Frame | Baseline; Weeks 24 to 36 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Mean Monthly Dose of Intravenous (IV) Elemental Iron Administered in Participants Who Have Received IV Iron |
---|---|
Description | |
Time Frame | Up to Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Proportion of Participants Receiving IV Iron Therapy |
---|---|
Description | |
Time Frame | Up to Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | Exploratory - Proportion of Participants Receiving Red Blood Cells (RBCs) Transfusion(s) |
---|---|
Description | |
Time Frame | Up to Week 52 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | Up to 208 weeks | |||
---|---|---|---|---|
Adverse Event Reporting Description | Treatment-emergent adverse events (TEAEs), defined as adverse events (AEs) that began (or pre-existing AEs that worsened) on or after the first dose through each participant's last participation date, were reported in study AKB-6548-CI-0015 (NCT02680574). Of the participants randomized, 1723 participants were included in the Safety population (861 and 862 participants in the Vadadustat and Darbepoetin alfa treatment groups, respectively). Two randomized participants did not receive treatment. | |||
Arm/Group Title | Vadadustat | Darbepoetin Alfa | ||
Arm/Group Description | Participants were randomized to receive Vadadustat at an initial oral dose of 300 milligrams per day (mg/day). Thereafter, Vadadustat was taken once daily on an outpatient basis. Up-and-down titration to 150, 300, 450, and 600 mg (available tablet strength was administered as the appropriate number of 150 mg tablets) was allowed during the study based on hemoglobin (Hb) level measurements to maintain target Hb levels. | Participants were randomized to Darbepoetin alfa at an initial dose that was based on the current package insert for investigational sites in the United States (US), and the Summary of Product Characteristics (SmPC) for all other investigational sites (non-US) for adult participants with chronic kidney disease not on dialysis. For participants already on Darbepoetin alfa, the initial dosing regimen in the study was based on the prior dosing regimen. | ||
All Cause Mortality |
||||
Vadadustat | Darbepoetin Alfa | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 139/861 (16.1%) | 139/862 (16.1%) | ||
Serious Adverse Events |
||||
Vadadustat | Darbepoetin Alfa | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 504/861 (58.5%) | 488/862 (56.6%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 16/861 (1.9%) | 18/862 (2.1%) | ||
Blood loss anaemia | 2/861 (0.2%) | 4/862 (0.5%) | ||
Nephrogenic anaemia | 1/861 (0.1%) | 3/862 (0.3%) | ||
Thrombocytopenia | 2/861 (0.2%) | 1/862 (0.1%) | ||
Immune thrombocytopenia | 0/861 (0%) | 2/862 (0.2%) | ||
Iron deficiency anaemia | 1/861 (0.1%) | 1/862 (0.1%) | ||
Bone marrow failure | 1/861 (0.1%) | 0/862 (0%) | ||
Coagulopathy | 0/861 (0%) | 1/862 (0.1%) | ||
Pancytopenia | 1/861 (0.1%) | 0/862 (0%) | ||
Cardiac disorders | ||||
Cardiac failure congestive | 29/861 (3.4%) | 31/862 (3.6%) | ||
Acute myocardial infarction | 34/861 (3.9%) | 24/862 (2.8%) | ||
Cardiac failure acute | 15/861 (1.7%) | 16/862 (1.9%) | ||
Atrial fibrillation | 16/861 (1.9%) | 13/862 (1.5%) | ||
Cardiac failure | 10/861 (1.2%) | 19/862 (2.2%) | ||
Cardiac arrest | 9/861 (1%) | 16/862 (1.9%) | ||
Coronary artery disease | 7/861 (0.8%) | 9/862 (1%) | ||
Cardiac failure chronic | 7/861 (0.8%) | 7/862 (0.8%) | ||
Acute left ventricular failure | 5/861 (0.6%) | 6/862 (0.7%) | ||
Myocardial infarction | 7/861 (0.8%) | 4/862 (0.5%) | ||
Left ventricular failure | 3/861 (0.3%) | 7/862 (0.8%) | ||
Angina unstable | 3/861 (0.3%) | 6/862 (0.7%) | ||
Atrial flutter | 2/861 (0.2%) | 5/862 (0.6%) | ||
Cardio-respiratory arrest | 3/861 (0.3%) | 4/862 (0.5%) | ||
Bradycardia | 4/861 (0.5%) | 2/862 (0.2%) | ||
Cardiogenic shock | 2/861 (0.2%) | 4/862 (0.5%) | ||
Cardiorenal syndrome | 4/861 (0.5%) | 2/862 (0.2%) | ||
Angina pectoris | 1/861 (0.1%) | 3/862 (0.3%) | ||
Cardiopulmonary failure | 3/861 (0.3%) | 1/862 (0.1%) | ||
Myocardial ischaemia | 2/861 (0.2%) | 2/862 (0.2%) | ||
Atrioventricular block | 1/861 (0.1%) | 2/862 (0.2%) | ||
Atrioventricular block complete | 1/861 (0.1%) | 2/862 (0.2%) | ||
Atrioventricular block second degree | 1/861 (0.1%) | 2/862 (0.2%) | ||
Coronary artery stenosis | 1/861 (0.1%) | 2/862 (0.2%) | ||
Pericardial effusion | 2/861 (0.2%) | 1/862 (0.1%) | ||
Pericarditis | 1/861 (0.1%) | 2/862 (0.2%) | ||
Ventricular fibrillation | 1/861 (0.1%) | 2/862 (0.2%) | ||
Acute coronary syndrome | 2/861 (0.2%) | 0/862 (0%) | ||
Arrhythmia | 2/861 (0.2%) | 0/862 (0%) | ||
Cardiomyopathy | 1/861 (0.1%) | 1/862 (0.1%) | ||
Sinus node dysfunction | 0/861 (0%) | 2/862 (0.2%) | ||
Ventricular tachycardia | 0/861 (0%) | 2/862 (0.2%) | ||
Bradyarrhythmia | 0/861 (0%) | 1/862 (0.1%) | ||
Cardiac tamponade | 0/861 (0%) | 1/862 (0.1%) | ||
Cardiac valve disease | 0/861 (0%) | 1/862 (0.1%) | ||
Heart valve incompetence | 0/861 (0%) | 1/862 (0.1%) | ||
Ischaemic cardiomyopathy | 0/861 (0%) | 1/862 (0.1%) | ||
Mitral valve calcification | 0/861 (0%) | 1/862 (0.1%) | ||
Mitral valve incompetence | 0/861 (0%) | 1/862 (0.1%) | ||
Pericarditis uraemic | 0/861 (0%) | 1/862 (0.1%) | ||
Pulseless electrical activity | 0/861 (0%) | 1/862 (0.1%) | ||
Right ventricular failure | 0/861 (0%) | 1/862 (0.1%) | ||
Tachycardia induced cardiomyopathy | 1/861 (0.1%) | 0/862 (0%) | ||
Tricuspid valve incompetence | 0/861 (0%) | 1/862 (0.1%) | ||
Ventricular hypokinesia | 1/861 (0.1%) | 0/862 (0%) | ||
Ear and labyrinth disorders | ||||
Vertigo | 1/861 (0.1%) | 2/862 (0.2%) | ||
Vertigo positional | 1/861 (0.1%) | 1/862 (0.1%) | ||
Endocrine disorders | ||||
Hypothyroidism | 2/861 (0.2%) | 1/862 (0.1%) | ||
Adrenal insufficiency | 2/861 (0.2%) | 0/862 (0%) | ||
Eye disorders | ||||
Cataract diabetic | 1/861 (0.1%) | 0/862 (0%) | ||
Tractional retinal detachment | 1/861 (0.1%) | 0/862 (0%) | ||
Gastrointestinal disorders | ||||
Gastrointestinal haemorrhage | 7/861 (0.8%) | 6/862 (0.7%) | ||
Upper gastrointestinal haemorrhage | 6/861 (0.7%) | 3/862 (0.3%) | ||
Vomiting | 3/861 (0.3%) | 4/862 (0.5%) | ||
Diarrhoea | 4/861 (0.5%) | 2/862 (0.2%) | ||
Pancreatitis acute | 3/861 (0.3%) | 2/862 (0.2%) | ||
Colitis | 3/861 (0.3%) | 1/862 (0.1%) | ||
Gastritis | 3/861 (0.3%) | 1/862 (0.1%) | ||
Lower gastrointestinal haemorrhage | 2/861 (0.2%) | 2/862 (0.2%) | ||
Abdominal pain | 2/861 (0.2%) | 1/862 (0.1%) | ||
Chronic gastritis | 1/861 (0.1%) | 2/862 (0.2%) | ||
Duodenal ulcer haemorrhage | 1/861 (0.1%) | 2/862 (0.2%) | ||
Intestinal obstruction | 2/861 (0.2%) | 1/862 (0.1%) | ||
Rectal haemorrhage | 3/861 (0.3%) | 0/862 (0%) | ||
Small intestinal obstruction | 1/861 (0.1%) | 2/862 (0.2%) | ||
Abdominal pain upper | 2/861 (0.2%) | 0/862 (0%) | ||
Constipation | 1/861 (0.1%) | 1/862 (0.1%) | ||
Faecaloma | 0/861 (0%) | 2/862 (0.2%) | ||
Gastric haemorrhage | 1/861 (0.1%) | 1/862 (0.1%) | ||
Gastric ulcer | 1/861 (0.1%) | 1/862 (0.1%) | ||
Gastritis erosive | 1/861 (0.1%) | 1/862 (0.1%) | ||
Gastrointestinal vascular malformation haemorrhagic | 1/861 (0.1%) | 1/862 (0.1%) | ||
Haemorrhagic erosive gastritis | 0/861 (0%) | 2/862 (0.2%) | ||
Incarcerated inguinal hernia | 1/861 (0.1%) | 1/862 (0.1%) | ||
Large intestine perforation | 1/861 (0.1%) | 1/862 (0.1%) | ||
Peptic ulcer | 2/861 (0.2%) | 0/862 (0%) | ||
Pharyngo-oesophageal diverticulum | 1/861 (0.1%) | 1/862 (0.1%) | ||
Small intestinal haemorrhage | 1/861 (0.1%) | 1/862 (0.1%) | ||
Abdominal pain lower | 1/861 (0.1%) | 0/862 (0%) | ||
Colitis ischaemic | 1/861 (0.1%) | 0/862 (0%) | ||
Cyclic vomiting syndrome | 0/861 (0%) | 1/862 (0.1%) | ||
Diabetic gastroparesis | 1/861 (0.1%) | 0/862 (0%) | ||
Diverticulum intestinal haemorrhagic | 0/861 (0%) | 1/862 (0.1%) | ||
Duodenal ulcer | 1/861 (0.1%) | 0/862 (0%) | ||
Duodenitis | 1/861 (0.1%) | 0/862 (0%) | ||
Dyschezia | 1/861 (0.1%) | 0/862 (0%) | ||
Femoral hernia incarcerated | 0/861 (0%) | 1/862 (0.1%) | ||
Gastric antral vascular ectasia | 1/861 (0.1%) | 0/862 (0%) | ||
Gastric perforation | 1/861 (0.1%) | 0/862 (0%) | ||
Gastric ulcer haemorrhage | 0/861 (0%) | 1/862 (0.1%) | ||
Gastrointestinal angiectasia | 0/861 (0%) | 1/862 (0.1%) | ||
Gastrointestinal inflammation | 1/861 (0.1%) | 0/862 (0%) | ||
Gastrointestinal polyp haemorrhage | 0/861 (0%) | 1/862 (0.1%) | ||
Gastrooesophageal reflux disease | 1/861 (0.1%) | 0/862 (0%) | ||
Gingival bleeding | 1/861 (0.1%) | 0/862 (0%) | ||
Haematemesis | 1/861 (0.1%) | 0/862 (0%) | ||
Haematochezia | 1/861 (0.1%) | 0/862 (0%) | ||
Haemorrhoidal haemorrhage | 1/861 (0.1%) | 0/862 (0%) | ||
Intestinal perforation | 0/861 (0%) | 1/862 (0.1%) | ||
Large intestinal haemorrhage | 1/861 (0.1%) | 0/862 (0%) | ||
Large intestine polyp | 0/861 (0%) | 1/862 (0.1%) | ||
Nausea | 0/861 (0%) | 1/862 (0.1%) | ||
Obstructive pancreatitis | 0/861 (0%) | 1/862 (0.1%) | ||
Oedematous pancreatitis | 1/861 (0.1%) | 0/862 (0%) | ||
Oesophageal ulcer haemorrhage | 0/861 (0%) | 1/862 (0.1%) | ||
Oesophageal varices haemorrhage | 1/861 (0.1%) | 0/862 (0%) | ||
Pancreatic mass | 0/861 (0%) | 1/862 (0.1%) | ||
Pancreatitis | 0/861 (0%) | 1/862 (0.1%) | ||
Pneumatosis intestinalis | 0/861 (0%) | 1/862 (0.1%) | ||
Portal hypertensive gastropathy | 1/861 (0.1%) | 0/862 (0%) | ||
Proctitis | 0/861 (0%) | 1/862 (0.1%) | ||
Small intestinal perforation | 1/861 (0.1%) | 0/862 (0%) | ||
Umbilical hernia | 0/861 (0%) | 1/862 (0.1%) | ||
Varices oesophageal | 0/861 (0%) | 1/862 (0.1%) | ||
General disorders | ||||
Death | 20/861 (2.3%) | 13/862 (1.5%) | ||
Multiple organ dysfunction syndrome | 4/861 (0.5%) | 3/862 (0.3%) | ||
Non-cardiac chest pain | 5/861 (0.6%) | 2/862 (0.2%) | ||
Asthenia | 1/861 (0.1%) | 5/862 (0.6%) | ||
Chest pain | 1/861 (0.1%) | 3/862 (0.3%) | ||
Generalised oedema | 2/861 (0.2%) | 2/862 (0.2%) | ||
Catheter site haemorrhage | 1/861 (0.1%) | 2/862 (0.2%) | ||
Complication associated with device | 3/861 (0.3%) | 0/862 (0%) | ||
Oedema peripheral | 1/861 (0.1%) | 2/862 (0.2%) | ||
Pyrexia | 3/861 (0.3%) | 0/862 (0%) | ||
General physical health deterioration | 2/861 (0.2%) | 0/862 (0%) | ||
Sudden death | 1/861 (0.1%) | 1/862 (0.1%) | ||
Chest discomfort | 1/861 (0.1%) | 0/862 (0%) | ||
Fatigue | 1/861 (0.1%) | 0/862 (0%) | ||
Hypothermia | 0/861 (0%) | 1/862 (0.1%) | ||
Impaired healing | 0/861 (0%) | 1/862 (0.1%) | ||
Malaise | 1/861 (0.1%) | 0/862 (0%) | ||
Sudden cardiac death | 1/861 (0.1%) | 0/862 (0%) | ||
Systemic inflammatory response syndrome | 1/861 (0.1%) | 0/862 (0%) | ||
Treatment noncompliance | 0/861 (0%) | 1/862 (0.1%) | ||
Hepatobiliary disorders | ||||
Cholecystitis acute | 3/861 (0.3%) | 3/862 (0.3%) | ||
Cholelithiasis | 2/861 (0.2%) | 1/862 (0.1%) | ||
Drug-induced liver injury | 2/861 (0.2%) | 1/862 (0.1%) | ||
Acute hepatic failure | 1/861 (0.1%) | 1/862 (0.1%) | ||
Cholecystitis | 2/861 (0.2%) | 0/862 (0%) | ||
Cholecystitis chronic | 0/861 (0%) | 2/862 (0.2%) | ||
Liver injury | 1/861 (0.1%) | 1/862 (0.1%) | ||
Chronic hepatic failure | 1/861 (0.1%) | 0/862 (0%) | ||
Gallbladder rupture | 0/861 (0%) | 1/862 (0.1%) | ||
Granulomatous liver disease | 0/861 (0%) | 1/862 (0.1%) | ||
Hepatitis alcoholic | 1/861 (0.1%) | 0/862 (0%) | ||
Hepatocellular injury | 1/861 (0.1%) | 0/862 (0%) | ||
Ischaemic hepatitis | 1/861 (0.1%) | 0/862 (0%) | ||
Non-alcoholic steatohepatitis | 0/861 (0%) | 1/862 (0.1%) | ||
Steatohepatitis | 1/861 (0.1%) | 0/862 (0%) | ||
Immune system disorders | ||||
Drug hypersensitivity | 1/861 (0.1%) | 2/862 (0.2%) | ||
Kidney transplant rejection | 0/861 (0%) | 2/862 (0.2%) | ||
Transplant rejection | 2/861 (0.2%) | 0/862 (0%) | ||
Infections and infestations | ||||
Pneumonia | 56/861 (6.5%) | 49/862 (5.7%) | ||
Urinary tract infection | 20/861 (2.3%) | 20/862 (2.3%) | ||
Sepsis | 17/861 (2%) | 16/862 (1.9%) | ||
Cellulitis | 6/861 (0.7%) | 17/862 (2%) | ||
Septic shock | 10/861 (1.2%) | 7/862 (0.8%) | ||
Osteomyelitis | 5/861 (0.6%) | 6/862 (0.7%) | ||
Clostridium difficile colitis | 8/861 (0.9%) | 2/862 (0.2%) | ||
Urosepsis | 6/861 (0.7%) | 4/862 (0.5%) | ||
Pyelonephritis acute | 3/861 (0.3%) | 5/862 (0.6%) | ||
Gangrene | 3/861 (0.3%) | 4/862 (0.5%) | ||
Gastroenteritis | 3/861 (0.3%) | 4/862 (0.5%) | ||
Peritonitis | 4/861 (0.5%) | 3/862 (0.3%) | ||
Pyelonephritis chronic | 4/861 (0.5%) | 3/862 (0.3%) | ||
Influenza | 3/861 (0.3%) | 3/862 (0.3%) | ||
Pyelonephritis | 4/861 (0.5%) | 2/862 (0.2%) | ||
Device related infection | 2/861 (0.2%) | 3/862 (0.3%) | ||
Diverticulitis | 3/861 (0.3%) | 2/862 (0.2%) | ||
Staphylococcal sepsis | 1/861 (0.1%) | 4/862 (0.5%) | ||
Bronchitis | 3/861 (0.3%) | 1/862 (0.1%) | ||
Cystitis | 2/861 (0.2%) | 2/862 (0.2%) | ||
Device related sepsis | 2/861 (0.2%) | 2/862 (0.2%) | ||
Peritonitis bacterial | 2/861 (0.2%) | 2/862 (0.2%) | ||
Pneumonia bacterial | 2/861 (0.2%) | 2/862 (0.2%) | ||
Staphylococcal bacteraemia | 0/861 (0%) | 4/862 (0.5%) | ||
Upper respiratory tract infection | 3/861 (0.3%) | 1/862 (0.1%) | ||
Urinary tract infection bacterial | 3/861 (0.3%) | 1/862 (0.1%) | ||
Abscess limb | 2/861 (0.2%) | 1/862 (0.1%) | ||
Anal abscess | 2/861 (0.2%) | 1/862 (0.1%) | ||
Appendicitis | 0/861 (0%) | 3/862 (0.3%) | ||
Arteriovenous fistula site infection | 1/861 (0.1%) | 2/862 (0.2%) | ||
Diabetic foot infection | 2/861 (0.2%) | 1/862 (0.1%) | ||
Escherichia urinary tract infection | 1/861 (0.1%) | 2/862 (0.2%) | ||
Infective exacerbation of bronchiectasis | 0/861 (0%) | 3/862 (0.3%) | ||
Viral infection | 1/861 (0.1%) | 2/862 (0.2%) | ||
Bacteraemia | 0/861 (0%) | 2/862 (0.2%) | ||
Clostridium difficile infection | 2/861 (0.2%) | 0/862 (0%) | ||
Endocarditis | 1/861 (0.1%) | 1/862 (0.1%) | ||
Escherichia bacteraemia | 0/861 (0%) | 2/862 (0.2%) | ||
Escherichia sepsis | 0/861 (0%) | 2/862 (0.2%) | ||
Intervertebral discitis | 2/861 (0.2%) | 0/862 (0%) | ||
Lower respiratory tract infection | 0/861 (0%) | 2/862 (0.2%) | ||
Pneumococcal sepsis | 1/861 (0.1%) | 1/862 (0.1%) | ||
Pneumonia staphylococcal | 2/861 (0.2%) | 0/862 (0%) | ||
Pulmonary sepsis | 1/861 (0.1%) | 1/862 (0.1%) | ||
Sinusitis | 1/861 (0.1%) | 1/862 (0.1%) | ||
Staphylococcal infection | 1/861 (0.1%) | 1/862 (0.1%) | ||
Abdominal wall abscess | 0/861 (0%) | 1/862 (0.1%) | ||
Abscess neck | 0/861 (0%) | 1/862 (0.1%) | ||
Acute hepatitis C | 1/861 (0.1%) | 0/862 (0%) | ||
Appendicitis perforated | 1/861 (0.1%) | 0/862 (0%) | ||
Atypical pneumonia | 1/861 (0.1%) | 0/862 (0%) | ||
Bacterial sepsis | 1/861 (0.1%) | 0/862 (0%) | ||
Biliary sepsis | 1/861 (0.1%) | 0/862 (0%) | ||
Bronchitis viral | 0/861 (0%) | 1/862 (0.1%) | ||
COVID-19 | 1/861 (0.1%) | 0/862 (0%) | ||
Campylobacter gastroenteritis | 1/861 (0.1%) | 0/862 (0%) | ||
Candida infection | 0/861 (0%) | 1/862 (0.1%) | ||
Cardiac valve vegetation | 0/861 (0%) | 1/862 (0.1%) | ||
Catheter bacteraemia | 0/861 (0%) | 1/862 (0.1%) | ||
Catheter site cellulitis | 1/861 (0.1%) | 0/862 (0%) | ||
Cryptosporidiosis infection | 1/861 (0.1%) | 0/862 (0%) | ||
Cystitis bacterial | 0/861 (0%) | 1/862 (0.1%) | ||
Cystitis klebsiella | 1/861 (0.1%) | 0/862 (0%) | ||
Cytomegalovirus infection | 1/861 (0.1%) | 0/862 (0%) | ||
Endocarditis bacterial | 0/861 (0%) | 1/862 (0.1%) | ||
Endocarditis staphylococcal | 0/861 (0%) | 1/862 (0.1%) | ||
Enterobacter infection | 0/861 (0%) | 1/862 (0.1%) | ||
Enterocolitis bacterial | 1/861 (0.1%) | 0/862 (0%) | ||
Escherichia infection | 0/861 (0%) | 1/862 (0.1%) | ||
Escherichia pyelonephritis | 0/861 (0%) | 1/862 (0.1%) | ||
Fournier's gangrene | 0/861 (0%) | 1/862 (0.1%) | ||
Fungal peritonitis | 0/861 (0%) | 1/862 (0.1%) | ||
Furuncle | 0/861 (0%) | 1/862 (0.1%) | ||
Gastritis viral | 1/861 (0.1%) | 0/862 (0%) | ||
Gastroenteritis clostridial | 1/861 (0.1%) | 0/862 (0%) | ||
Gastroenteritis viral | 1/861 (0.1%) | 0/862 (0%) | ||
Gastrointestinal infection | 0/861 (0%) | 1/862 (0.1%) | ||
Haematoma infection | 1/861 (0.1%) | 0/862 (0%) | ||
Helicobacter gastritis | 1/861 (0.1%) | 0/862 (0%) | ||
Infected skin ulcer | 1/861 (0.1%) | 0/862 (0%) | ||
Infection | 1/861 (0.1%) | 0/862 (0%) | ||
Intestinal sepsis | 1/861 (0.1%) | 0/862 (0%) | ||
Klebsiella infection | 1/861 (0.1%) | 0/862 (0%) | ||
Localised infection | 1/861 (0.1%) | 0/862 (0%) | ||
Mastoiditis | 1/861 (0.1%) | 0/862 (0%) | ||
Osteomyelitis bacterial | 1/861 (0.1%) | 0/862 (0%) | ||
Parainfluenzae virus infection | 1/861 (0.1%) | 0/862 (0%) | ||
Parotid abscess | 0/861 (0%) | 1/862 (0.1%) | ||
Perirectal abscess | 1/861 (0.1%) | 0/862 (0%) | ||
Pharyngeal abscess | 0/861 (0%) | 1/862 (0.1%) | ||
Pneumonia escherichia | 0/861 (0%) | 1/862 (0.1%) | ||
Pneumonia influenzal | 0/861 (0%) | 1/862 (0.1%) | ||
Pneumonia klebsiella | 0/861 (0%) | 1/862 (0.1%) | ||
Pneumonia legionella | 1/861 (0.1%) | 0/862 (0%) | ||
Pneumonia respiratory syncytial viral | 1/861 (0.1%) | 0/862 (0%) | ||
Pneumonia viral | 0/861 (0%) | 1/862 (0.1%) | ||
Post procedural cellulitis | 1/861 (0.1%) | 0/862 (0%) | ||
Post procedural infection | 1/861 (0.1%) | 0/862 (0%) | ||
Proteus infection | 0/861 (0%) | 1/862 (0.1%) | ||
Pseudomonal bacteraemia | 1/861 (0.1%) | 0/862 (0%) | ||
Pulmonary tuberculosis | 1/861 (0.1%) | 0/862 (0%) | ||
Pyonephrosis | 1/861 (0.1%) | 0/862 (0%) | ||
Renal graft infection | 1/861 (0.1%) | 0/862 (0%) | ||
Respiratory tract infection | 0/861 (0%) | 1/862 (0.1%) | ||
Salmonella bacteraemia | 1/861 (0.1%) | 0/862 (0%) | ||
Scarlet fever | 1/861 (0.1%) | 0/862 (0%) | ||
Scrotal abscess | 1/861 (0.1%) | 0/862 (0%) | ||
Serratia bacteraemia | 0/861 (0%) | 1/862 (0.1%) | ||
Shunt infection | 0/861 (0%) | 1/862 (0.1%) | ||
Tinea pedis | 0/861 (0%) | 1/862 (0.1%) | ||
Tooth abscess | 1/861 (0.1%) | 0/862 (0%) | ||
Tracheitis | 0/861 (0%) | 1/862 (0.1%) | ||
Tracheobronchitis | 1/861 (0.1%) | 0/862 (0%) | ||
Urinary tract infection pseudomonal | 1/861 (0.1%) | 0/862 (0%) | ||
Vestibular neuronitis | 1/861 (0.1%) | 0/862 (0%) | ||
Viral diarrhoea | 1/861 (0.1%) | 0/862 (0%) | ||
Viral upper respiratory tract infection | 1/861 (0.1%) | 0/862 (0%) | ||
Wound infection | 0/861 (0%) | 1/862 (0.1%) | ||
Wound infection pseudomonas | 0/861 (0%) | 1/862 (0.1%) | ||
Injury, poisoning and procedural complications | ||||
Fall | 8/861 (0.9%) | 12/862 (1.4%) | ||
Hip fracture | 12/861 (1.4%) | 2/862 (0.2%) | ||
Arteriovenous fistula thrombosis | 1/861 (0.1%) | 7/862 (0.8%) | ||
Femoral neck fracture | 4/861 (0.5%) | 3/862 (0.3%) | ||
Arteriovenous fistula site complication | 2/861 (0.2%) | 3/862 (0.3%) | ||
Wrist fracture | 2/861 (0.2%) | 2/862 (0.2%) | ||
Femur fracture | 1/861 (0.1%) | 2/862 (0.2%) | ||
Humerus fracture | 1/861 (0.1%) | 2/862 (0.2%) | ||
Lower limb fracture | 2/861 (0.2%) | 1/862 (0.1%) | ||
Rib fracture | 0/861 (0%) | 3/862 (0.3%) | ||
Spinal compression fracture | 1/861 (0.1%) | 2/862 (0.2%) | ||
Subdural haematoma | 0/861 (0%) | 3/862 (0.3%) | ||
Tibia fracture | 2/861 (0.2%) | 1/862 (0.1%) | ||
Toxicity to various agents | 2/861 (0.2%) | 1/862 (0.1%) | ||
Wound dehiscence | 1/861 (0.1%) | 2/862 (0.2%) | ||
Accidental overdose | 2/861 (0.2%) | 0/862 (0%) | ||
Ankle fracture | 2/861 (0.2%) | 0/862 (0%) | ||
Arteriovenous fistula maturation failure | 2/861 (0.2%) | 0/862 (0%) | ||
Arteriovenous fistula site haematoma | 0/861 (0%) | 2/862 (0.2%) | ||
Head injury | 1/861 (0.1%) | 1/862 (0.1%) | ||
Joint dislocation | 0/861 (0%) | 2/862 (0.2%) | ||
Multiple injuries | 2/861 (0.2%) | 0/862 (0%) | ||
Road traffic accident | 1/861 (0.1%) | 1/862 (0.1%) | ||
Traumatic intracranial haemorrhage | 1/861 (0.1%) | 1/862 (0.1%) | ||
Upper limb fracture | 2/861 (0.2%) | 0/862 (0%) | ||
Animal bite | 0/861 (0%) | 1/862 (0.1%) | ||
Arteriovenous fistula aneurysm | 0/861 (0%) | 1/862 (0.1%) | ||
Arteriovenous fistula site haemorrhage | 0/861 (0%) | 1/862 (0.1%) | ||
Brain contusion | 1/861 (0.1%) | 0/862 (0%) | ||
Chest injury | 0/861 (0%) | 1/862 (0.1%) | ||
Comminuted fracture | 1/861 (0.1%) | 0/862 (0%) | ||
Complications of transplanted kidney | 1/861 (0.1%) | 0/862 (0%) | ||
Concussion | 0/861 (0%) | 1/862 (0.1%) | ||
Contusion | 0/861 (0%) | 1/862 (0.1%) | ||
Craniocerebral injury | 1/861 (0.1%) | 0/862 (0%) | ||
Device placement issue | 1/861 (0.1%) | 0/862 (0%) | ||
Eye contusion | 1/861 (0.1%) | 0/862 (0%) | ||
Facial bones fracture | 1/861 (0.1%) | 0/862 (0%) | ||
Fibula fracture | 1/861 (0.1%) | 0/862 (0%) | ||
Foot fracture | 0/861 (0%) | 1/862 (0.1%) | ||
Forearm fracture | 1/861 (0.1%) | 0/862 (0%) | ||
Fractured sacrum | 0/861 (0%) | 1/862 (0.1%) | ||
Multiple fractures | 1/861 (0.1%) | 0/862 (0%) | ||
Muscle strain | 0/861 (0%) | 1/862 (0.1%) | ||
Pelvic fracture | 0/861 (0%) | 1/862 (0.1%) | ||
Periorbital haematoma | 0/861 (0%) | 1/862 (0.1%) | ||
Peritoneal dialysis complication | 1/861 (0.1%) | 0/862 (0%) | ||
Post procedural haematuria | 1/861 (0.1%) | 0/862 (0%) | ||
Radiation pneumonitis | 0/861 (0%) | 1/862 (0.1%) | ||
Radius fracture | 0/861 (0%) | 1/862 (0.1%) | ||
Shunt malfunction | 0/861 (0%) | 1/862 (0.1%) | ||
Shunt occlusion | 1/861 (0.1%) | 0/862 (0%) | ||
Shunt thrombosis | 0/861 (0%) | 1/862 (0.1%) | ||
Skin laceration | 0/861 (0%) | 1/862 (0.1%) | ||
Spinal fracture | 0/861 (0%) | 1/862 (0.1%) | ||
Tendon injury | 1/861 (0.1%) | 0/862 (0%) | ||
Thoracic vertebral fracture | 0/861 (0%) | 1/862 (0.1%) | ||
Traumatic haematoma | 0/861 (0%) | 1/862 (0.1%) | ||
Ulna fracture | 0/861 (0%) | 1/862 (0.1%) | ||
Vascular access site haematoma | 0/861 (0%) | 1/862 (0.1%) | ||
Vascular access site thrombosis | 1/861 (0.1%) | 0/862 (0%) | ||
Wound evisceration | 0/861 (0%) | 1/862 (0.1%) | ||
Investigations | ||||
Alanine aminotransferase increased | 7/861 (0.8%) | 8/862 (0.9%) | ||
Aspartate aminotransferase increased | 4/861 (0.5%) | 6/862 (0.7%) | ||
Hepatic enzyme increased | 1/861 (0.1%) | 3/862 (0.3%) | ||
Transaminases increased | 1/861 (0.1%) | 3/862 (0.3%) | ||
Blood potassium increased | 0/861 (0%) | 2/862 (0.2%) | ||
International normalised ratio increased | 2/861 (0.2%) | 0/862 (0%) | ||
Anticoagulation drug level below therapeutic | 0/861 (0%) | 1/862 (0.1%) | ||
Blood bilirubin increased | 1/861 (0.1%) | 0/862 (0%) | ||
Blood glucose fluctuation | 1/861 (0.1%) | 0/862 (0%) | ||
Blood pressure increased | 0/861 (0%) | 1/862 (0.1%) | ||
Electrocardiogram repolarisation abnormality | 0/861 (0%) | 1/862 (0.1%) | ||
Glomerular filtration rate decreased | 1/861 (0.1%) | 0/862 (0%) | ||
Prothrombin time prolonged | 0/861 (0%) | 1/862 (0.1%) | ||
Weight decreased | 1/861 (0.1%) | 0/862 (0%) | ||
Metabolism and nutrition disorders | ||||
Fluid overload | 17/861 (2%) | 12/862 (1.4%) | ||
Dehydration | 16/861 (1.9%) | 10/862 (1.2%) | ||
Hyperkalaemia | 13/861 (1.5%) | 9/862 (1%) | ||
Hypoglycaemia | 13/861 (1.5%) | 6/862 (0.7%) | ||
Diabetic ketoacidosis | 4/861 (0.5%) | 5/862 (0.6%) | ||
Diabetes mellitus | 3/861 (0.3%) | 5/862 (0.6%) | ||
Hyponatraemia | 2/861 (0.2%) | 6/862 (0.7%) | ||
Hypovolaemia | 3/861 (0.3%) | 5/862 (0.6%) | ||
Hyperglycaemia | 3/861 (0.3%) | 4/862 (0.5%) | ||
Hypervolaemia | 4/861 (0.5%) | 3/862 (0.3%) | ||
Diabetic metabolic decompensation | 3/861 (0.3%) | 2/862 (0.2%) | ||
Metabolic acidosis | 3/861 (0.3%) | 1/862 (0.1%) | ||
Diabetes mellitus inadequate control | 1/861 (0.1%) | 2/862 (0.2%) | ||
Gout | 2/861 (0.2%) | 1/862 (0.1%) | ||
Hypokalaemia | 2/861 (0.2%) | 1/862 (0.1%) | ||
Malnutrition | 1/861 (0.1%) | 1/862 (0.1%) | ||
Obesity | 2/861 (0.2%) | 0/862 (0%) | ||
Acidosis | 0/861 (0%) | 1/862 (0.1%) | ||
Cachexia | 0/861 (0%) | 1/862 (0.1%) | ||
Decreased appetite | 1/861 (0.1%) | 0/862 (0%) | ||
Electrolyte imbalance | 1/861 (0.1%) | 0/862 (0%) | ||
Failure to thrive | 0/861 (0%) | 1/862 (0.1%) | ||
Hypercalcaemia | 0/861 (0%) | 1/862 (0.1%) | ||
Hyperglycaemic hyperosmolar nonketotic syndrome | 1/861 (0.1%) | 0/862 (0%) | ||
Hypomagnesaemia | 0/861 (0%) | 1/862 (0.1%) | ||
Type 2 diabetes mellitus | 0/861 (0%) | 1/862 (0.1%) | ||
Musculoskeletal and connective tissue disorders | ||||
Osteoarthritis | 5/861 (0.6%) | 6/862 (0.7%) | ||
Arthralgia | 3/861 (0.3%) | 0/862 (0%) | ||
Rhabdomyolysis | 3/861 (0.3%) | 0/862 (0%) | ||
Spinal osteoarthritis | 1/861 (0.1%) | 2/862 (0.2%) | ||
Spinal stenosis | 1/861 (0.1%) | 2/862 (0.2%) | ||
Arthritis | 1/861 (0.1%) | 1/862 (0.1%) | ||
Back pain | 1/861 (0.1%) | 1/862 (0.1%) | ||
Flank pain | 0/861 (0%) | 2/862 (0.2%) | ||
Polymyalgia rheumatica | 2/861 (0.2%) | 0/862 (0%) | ||
Spondylolisthesis | 1/861 (0.1%) | 1/862 (0.1%) | ||
Ankylosing spondylitis | 0/861 (0%) | 1/862 (0.1%) | ||
Bursitis | 1/861 (0.1%) | 0/862 (0%) | ||
Cervical spinal stenosis | 1/861 (0.1%) | 0/862 (0%) | ||
Chest wall haematoma | 0/861 (0%) | 1/862 (0.1%) | ||
Costochondritis | 1/861 (0.1%) | 0/862 (0%) | ||
Diabetic amyotrophy | 0/861 (0%) | 1/862 (0.1%) | ||
Groin pain | 1/861 (0.1%) | 0/862 (0%) | ||
Intervertebral disc degeneration | 0/861 (0%) | 1/862 (0.1%) | ||
Lumbar spinal stenosis | 0/861 (0%) | 1/862 (0.1%) | ||
Muscle spasms | 0/861 (0%) | 1/862 (0.1%) | ||
Musculoskeletal chest pain | 0/861 (0%) | 1/862 (0.1%) | ||
Musculoskeletal pain | 1/861 (0.1%) | 0/862 (0%) | ||
Myopathy endocrine | 0/861 (0%) | 1/862 (0.1%) | ||
Osteonecrosis | 0/861 (0%) | 1/862 (0.1%) | ||
Polyarthritis | 1/861 (0.1%) | 0/862 (0%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Plasma cell myeloma | 3/861 (0.3%) | 3/862 (0.3%) | ||
Basal cell carcinoma | 4/861 (0.5%) | 0/862 (0%) | ||
Invasive ductal breast carcinoma | 3/861 (0.3%) | 1/862 (0.1%) | ||
Prostate cancer | 1/861 (0.1%) | 3/862 (0.3%) | ||
Myelodysplastic syndrome | 2/861 (0.2%) | 1/862 (0.1%) | ||
Prostate cancer recurrent | 1/861 (0.1%) | 2/862 (0.2%) | ||
Adenocarcinoma of colon | 1/861 (0.1%) | 1/862 (0.1%) | ||
Breast cancer | 0/861 (0%) | 2/862 (0.2%) | ||
Hepatic cancer | 1/861 (0.1%) | 1/862 (0.1%) | ||
Lung neoplasm malignant | 0/861 (0%) | 2/862 (0.2%) | ||
Squamous cell carcinoma of skin | 2/861 (0.2%) | 0/862 (0%) | ||
Acute myeloid leukaemia | 0/861 (0%) | 1/862 (0.1%) | ||
Adenocarcinoma | 0/861 (0%) | 1/862 (0.1%) | ||
Adenocarcinoma gastric | 0/861 (0%) | 1/862 (0.1%) | ||
Adenocarcinoma pancreas | 0/861 (0%) | 1/862 (0.1%) | ||
Bladder cancer | 1/861 (0.1%) | 0/862 (0%) | ||
Bladder cancer recurrent | 0/861 (0%) | 1/862 (0.1%) | ||
Brain neoplasm | 0/861 (0%) | 1/862 (0.1%) | ||
Breast cancer metastatic | 0/861 (0%) | 1/862 (0.1%) | ||
Cancer pain | 1/861 (0.1%) | 0/862 (0%) | ||
Cerebellar tumour | 0/861 (0%) | 1/862 (0.1%) | ||
Cervix carcinoma | 1/861 (0.1%) | 0/862 (0%) | ||
Cholangiocarcinoma | 0/861 (0%) | 1/862 (0.1%) | ||
Clear cell renal cell carcinoma | 1/861 (0.1%) | 0/862 (0%) | ||
Colon cancer | 1/861 (0.1%) | 0/862 (0%) | ||
Gallbladder cancer | 1/861 (0.1%) | 0/862 (0%) | ||
Gastric cancer | 1/861 (0.1%) | 0/862 (0%) | ||
Gastric cancer stage IV | 0/861 (0%) | 1/862 (0.1%) | ||
Hairy cell leukaemia | 0/861 (0%) | 1/862 (0.1%) | ||
Hepatocellular carcinoma | 0/861 (0%) | 1/862 (0.1%) | ||
Lung cancer metastatic | 0/861 (0%) | 1/862 (0.1%) | ||
Lung neoplasm | 0/861 (0%) | 1/862 (0.1%) | ||
Metastases to central nervous system | 0/861 (0%) | 1/862 (0.1%) | ||
Metastatic bronchial carcinoma | 1/861 (0.1%) | 0/862 (0%) | ||
Neoplasm malignant | 1/861 (0.1%) | 0/862 (0%) | ||
Non-small cell lung cancer | 0/861 (0%) | 1/862 (0.1%) | ||
Non-small cell lung cancer stage I | 1/861 (0.1%) | 0/862 (0%) | ||
Oesophageal carcinoma | 0/861 (0%) | 1/862 (0.1%) | ||
Oesophageal squamous cell carcinoma | 1/861 (0.1%) | 0/862 (0%) | ||
Ovarian adenoma | 1/861 (0.1%) | 0/862 (0%) | ||
Pancreatic carcinoma metastatic | 1/861 (0.1%) | 0/862 (0%) | ||
Papillary thyroid cancer | 1/861 (0.1%) | 0/862 (0%) | ||
Renal cancer stage II | 1/861 (0.1%) | 0/862 (0%) | ||
Renal neoplasm | 0/861 (0%) | 1/862 (0.1%) | ||
Seborrhoeic keratosis | 1/861 (0.1%) | 0/862 (0%) | ||
Squamous cell carcinoma of pharynx | 1/861 (0.1%) | 0/862 (0%) | ||
Transitional cell carcinoma | 0/861 (0%) | 1/862 (0.1%) | ||
Nervous system disorders | ||||
Syncope | 6/861 (0.7%) | 9/862 (1%) | ||
Metabolic encephalopathy | 5/861 (0.6%) | 9/862 (1%) | ||
Cerebrovascular accident | 7/861 (0.8%) | 4/862 (0.5%) | ||
Ischaemic stroke | 8/861 (0.9%) | 2/862 (0.2%) | ||
Transient ischaemic attack | 6/861 (0.7%) | 3/862 (0.3%) | ||
Encephalopathy | 3/861 (0.3%) | 5/862 (0.6%) | ||
Haemorrhagic stroke | 3/861 (0.3%) | 1/862 (0.1%) | ||
Seizure | 2/861 (0.2%) | 2/862 (0.2%) | ||
Cerebral infarction | 0/861 (0%) | 2/862 (0.2%) | ||
Dementia | 1/861 (0.1%) | 1/862 (0.1%) | ||
Dizziness | 2/861 (0.2%) | 0/862 (0%) | ||
Ischaemic cerebral infarction | 1/861 (0.1%) | 1/862 (0.1%) | ||
Migraine | 1/861 (0.1%) | 1/862 (0.1%) | ||
Subarachnoid haemorrhage | 2/861 (0.2%) | 0/862 (0%) | ||
Toxic encephalopathy | 1/861 (0.1%) | 1/862 (0.1%) | ||
Uraemic encephalopathy | 2/861 (0.2%) | 0/862 (0%) | ||
Brain stem stroke | 0/861 (0%) | 1/862 (0.1%) | ||
Cerebellar infarction | 0/861 (0%) | 1/862 (0.1%) | ||
Cerebral artery thrombosis | 0/861 (0%) | 1/862 (0.1%) | ||
Cerebral haemorrhage | 1/861 (0.1%) | 0/862 (0%) | ||
Cerebral ischaemia | 0/861 (0%) | 1/862 (0.1%) | ||
Dementia Alzheimer's type | 1/861 (0.1%) | 0/862 (0%) | ||
Diabetic coma | 1/861 (0.1%) | 0/862 (0%) | ||
Diabetic encephalopathy | 1/861 (0.1%) | 0/862 (0%) | ||
Embolic cerebral infarction | 1/861 (0.1%) | 0/862 (0%) | ||
Haemorrhage intracranial | 1/861 (0.1%) | 0/862 (0%) | ||
Headache | 1/861 (0.1%) | 0/862 (0%) | ||
Hepatic encephalopathy | 0/861 (0%) | 1/862 (0.1%) | ||
Hypoglycaemic encephalopathy | 0/861 (0%) | 1/862 (0.1%) | ||
Hypoglycaemic unconsciousness | 0/861 (0%) | 1/862 (0.1%) | ||
Hypoxic-ischaemic encephalopathy | 1/861 (0.1%) | 0/862 (0%) | ||
Intraventricular haemorrhage | 0/861 (0%) | 1/862 (0.1%) | ||
Lacunar stroke | 0/861 (0%) | 1/862 (0.1%) | ||
Mental impairment | 0/861 (0%) | 1/862 (0.1%) | ||
Posterior reversible encephalopathy syndrome | 0/861 (0%) | 1/862 (0.1%) | ||
Presyncope | 1/861 (0.1%) | 0/862 (0%) | ||
Sciatica | 0/861 (0%) | 1/862 (0.1%) | ||
Status epilepticus | 1/861 (0.1%) | 0/862 (0%) | ||
Thalamic infarction | 1/861 (0.1%) | 0/862 (0%) | ||
Thrombotic stroke | 0/861 (0%) | 1/862 (0.1%) | ||
VIth nerve disorder | 0/861 (0%) | 1/862 (0.1%) | ||
Vertigo CNS origin | 0/861 (0%) | 1/862 (0.1%) | ||
Pregnancy, puerperium and perinatal conditions | ||||
Abortion spontaneous | 1/861 (0.1%) | 0/862 (0%) | ||
Product Issues | ||||
Device dislocation | 0/861 (0%) | 3/862 (0.3%) | ||
Device occlusion | 0/861 (0%) | 2/862 (0.2%) | ||
Psychiatric disorders | ||||
Mental status changes | 2/861 (0.2%) | 5/862 (0.6%) | ||
Depression | 1/861 (0.1%) | 3/862 (0.3%) | ||
Delirium | 2/861 (0.2%) | 1/862 (0.1%) | ||
Anger | 0/861 (0%) | 1/862 (0.1%) | ||
Anxiety | 0/861 (0%) | 1/862 (0.1%) | ||
Major depression | 1/861 (0.1%) | 0/862 (0%) | ||
Panic attack | 1/861 (0.1%) | 0/862 (0%) | ||
Psychotic disorder | 0/861 (0%) | 1/862 (0.1%) | ||
Schizophrenia | 0/861 (0%) | 1/862 (0.1%) | ||
Suicidal ideation | 0/861 (0%) | 1/862 (0.1%) | ||
Renal and urinary disorders | ||||
End stage renal disease | 232/861 (26.9%) | 238/862 (27.6%) | ||
Acute kidney injury | 34/861 (3.9%) | 32/862 (3.7%) | ||
Diabetic nephropathy | 6/861 (0.7%) | 6/862 (0.7%) | ||
Azotaemia | 4/861 (0.5%) | 6/862 (0.7%) | ||
Renal impairment | 3/861 (0.3%) | 4/862 (0.5%) | ||
Urinary tract obstruction | 3/861 (0.3%) | 2/862 (0.2%) | ||
Renal tubular necrosis | 3/861 (0.3%) | 1/862 (0.1%) | ||
Chronic kidney disease | 0/861 (0%) | 3/862 (0.3%) | ||
Glomerulonephritis | 2/861 (0.2%) | 1/862 (0.1%) | ||
Hydronephrosis | 2/861 (0.2%) | 1/862 (0.1%) | ||
Urethral stenosis | 0/861 (0%) | 3/862 (0.3%) | ||
Cystitis haemorrhagic | 2/861 (0.2%) | 0/862 (0%) | ||
Dysuria | 1/861 (0.1%) | 1/862 (0.1%) | ||
Haematuria | 1/861 (0.1%) | 1/862 (0.1%) | ||
Renal failure | 0/861 (0%) | 2/862 (0.2%) | ||
Urinary retention | 1/861 (0.1%) | 1/862 (0.1%) | ||
Acute phosphate nephropathy | 0/861 (0%) | 1/862 (0.1%) | ||
Calculus urinary | 0/861 (0%) | 1/862 (0.1%) | ||
Glomerulonephritis membranoproliferative | 1/861 (0.1%) | 0/862 (0%) | ||
Glomerulosclerosis | 1/861 (0.1%) | 0/862 (0%) | ||
Hypertensive nephropathy | 0/861 (0%) | 1/862 (0.1%) | ||
Nephrolithiasis | 1/861 (0.1%) | 0/862 (0%) | ||
Nephropathy toxic | 1/861 (0.1%) | 0/862 (0%) | ||
Nephrotic syndrome | 0/861 (0%) | 1/862 (0.1%) | ||
Neurogenic bladder | 1/861 (0.1%) | 0/862 (0%) | ||
Reflux nephropathy | 0/861 (0%) | 1/862 (0.1%) | ||
Renal mass | 1/861 (0.1%) | 0/862 (0%) | ||
Renal papillary necrosis | 1/861 (0.1%) | 0/862 (0%) | ||
Renal vascular thrombosis | 0/861 (0%) | 1/862 (0.1%) | ||
Ureteric obstruction | 1/861 (0.1%) | 0/862 (0%) | ||
Ureteric stenosis | 0/861 (0%) | 1/862 (0.1%) | ||
Reproductive system and breast disorders | ||||
Benign prostatic hyperplasia | 0/861 (0%) | 3/862 (0.3%) | ||
Uterine prolapse | 1/861 (0.1%) | 1/862 (0.1%) | ||
Cervical polyp | 1/861 (0.1%) | 0/862 (0%) | ||
Endometriosis | 1/861 (0.1%) | 0/862 (0%) | ||
Female genital tract fistula | 0/861 (0%) | 1/862 (0.1%) | ||
Prostatitis | 1/861 (0.1%) | 0/862 (0%) | ||
Uterine polyp | 0/861 (0%) | 1/862 (0.1%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Acute respiratory failure | 14/861 (1.6%) | 9/862 (1%) | ||
Chronic obstructive pulmonary disease | 10/861 (1.2%) | 7/862 (0.8%) | ||
Pulmonary oedema | 5/861 (0.6%) | 11/862 (1.3%) | ||
Pneumonia aspiration | 5/861 (0.6%) | 7/862 (0.8%) | ||
Respiratory failure | 4/861 (0.5%) | 7/862 (0.8%) | ||
Acute pulmonary oedema | 2/861 (0.2%) | 6/862 (0.7%) | ||
Pleural effusion | 1/861 (0.1%) | 7/862 (0.8%) | ||
Pulmonary hypertension | 4/861 (0.5%) | 3/862 (0.3%) | ||
Dyspnoea | 2/861 (0.2%) | 4/862 (0.5%) | ||
Pulmonary embolism | 3/861 (0.3%) | 3/862 (0.3%) | ||
Asthma | 2/861 (0.2%) | 1/862 (0.1%) | ||
Interstitial lung disease | 2/861 (0.2%) | 1/862 (0.1%) | ||
Bronchitis chronic | 1/861 (0.1%) | 1/862 (0.1%) | ||
Emphysema | 2/861 (0.2%) | 0/862 (0%) | ||
Epistaxis | 0/861 (0%) | 2/862 (0.2%) | ||
Pneumothorax | 1/861 (0.1%) | 1/862 (0.1%) | ||
Respiratory distress | 0/861 (0%) | 2/862 (0.2%) | ||
Aspiration | 0/861 (0%) | 1/862 (0.1%) | ||
Bronchiectasis | 0/861 (0%) | 1/862 (0.1%) | ||
Dyspnoea at rest | 0/861 (0%) | 1/862 (0.1%) | ||
Haemoptysis | 0/861 (0%) | 1/862 (0.1%) | ||
Hydrothorax | 0/861 (0%) | 1/862 (0.1%) | ||
Hypoxia | 0/861 (0%) | 1/862 (0.1%) | ||
Pleurisy | 1/861 (0.1%) | 0/862 (0%) | ||
Pleuritic pain | 1/861 (0.1%) | 0/862 (0%) | ||
Pneumothorax spontaneous | 0/861 (0%) | 1/862 (0.1%) | ||
Pulmonary arterial hypertension | 1/861 (0.1%) | 0/862 (0%) | ||
Respiratory acidosis | 1/861 (0.1%) | 0/862 (0%) | ||
Respiratory arrest | 0/861 (0%) | 1/862 (0.1%) | ||
Skin and subcutaneous tissue disorders | ||||
Diabetic foot | 5/861 (0.6%) | 5/862 (0.6%) | ||
Decubitus ulcer | 4/861 (0.5%) | 1/862 (0.1%) | ||
Neuropathic ulcer | 0/861 (0%) | 2/862 (0.2%) | ||
Capillaritis | 0/861 (0%) | 1/862 (0.1%) | ||
Hidradenitis | 1/861 (0.1%) | 0/862 (0%) | ||
Pemphigoid | 1/861 (0.1%) | 0/862 (0%) | ||
Pruritus | 0/861 (0%) | 1/862 (0.1%) | ||
Rash | 0/861 (0%) | 1/862 (0.1%) | ||
Rash maculo-papular | 0/861 (0%) | 1/862 (0.1%) | ||
Rash scarlatiniform | 1/861 (0.1%) | 0/862 (0%) | ||
Skin ulcer | 0/861 (0%) | 1/862 (0.1%) | ||
Vascular disorders | ||||
Hypertension | 8/861 (0.9%) | 9/862 (1%) | ||
Deep vein thrombosis | 5/861 (0.6%) | 7/862 (0.8%) | ||
Hypertensive emergency | 4/861 (0.5%) | 8/862 (0.9%) | ||
Hypertensive urgency | 4/861 (0.5%) | 5/862 (0.6%) | ||
Hypotension | 6/861 (0.7%) | 2/862 (0.2%) | ||
Hypertensive crisis | 0/861 (0%) | 6/862 (0.7%) | ||
Peripheral arterial occlusive disease | 3/861 (0.3%) | 3/862 (0.3%) | ||
Aortic stenosis | 2/861 (0.2%) | 2/862 (0.2%) | ||
Peripheral artery thrombosis | 4/861 (0.5%) | 0/862 (0%) | ||
Peripheral ischaemia | 4/861 (0.5%) | 0/862 (0%) | ||
Orthostatic hypotension | 2/861 (0.2%) | 1/862 (0.1%) | ||
Peripheral vascular disorder | 1/861 (0.1%) | 2/862 (0.2%) | ||
Arteriosclerosis | 1/861 (0.1%) | 1/862 (0.1%) | ||
Hypovolaemic shock | 2/861 (0.2%) | 0/862 (0%) | ||
Steal syndrome | 1/861 (0.1%) | 1/862 (0.1%) | ||
Venous thrombosis limb | 0/861 (0%) | 2/862 (0.2%) | ||
Accelerated hypertension | 0/861 (0%) | 1/862 (0.1%) | ||
Aortic aneurysm | 1/861 (0.1%) | 0/862 (0%) | ||
Axillary vein thrombosis | 0/861 (0%) | 1/862 (0.1%) | ||
Extremity necrosis | 0/861 (0%) | 1/862 (0.1%) | ||
Haematoma | 1/861 (0.1%) | 0/862 (0%) | ||
Lymphocele | 0/861 (0%) | 1/862 (0.1%) | ||
Lymphorrhoea | 1/861 (0.1%) | 0/862 (0%) | ||
Malignant hypertension | 1/861 (0.1%) | 0/862 (0%) | ||
Shock haemorrhagic | 1/861 (0.1%) | 0/862 (0%) | ||
Subclavian vein stenosis | 1/861 (0.1%) | 0/862 (0%) | ||
Vascular rupture | 1/861 (0.1%) | 0/862 (0%) | ||
Vascular stenosis | 0/861 (0%) | 1/862 (0.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
Vadadustat | Darbepoetin Alfa | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 482/861 (56%) | 436/862 (50.6%) | ||
Gastrointestinal disorders | ||||
Diarrhoea | 117/861 (13.6%) | 76/862 (8.8%) | ||
Nausea | 73/861 (8.5%) | 57/862 (6.6%) | ||
Constipation | 44/861 (5.1%) | 38/862 (4.4%) | ||
General disorders | ||||
Oedema peripheral | 84/861 (9.8%) | 85/862 (9.9%) | ||
Infections and infestations | ||||
Urinary tract infection | 93/861 (10.8%) | 113/862 (13.1%) | ||
Nasopharyngitis | 53/861 (6.2%) | 61/862 (7.1%) | ||
Upper respiratory tract infection | 55/861 (6.4%) | 44/862 (5.1%) | ||
Bronchitis | 44/861 (5.1%) | 32/862 (3.7%) | ||
Injury, poisoning and procedural complications | ||||
Fall | 64/861 (7.4%) | 53/862 (6.1%) | ||
Metabolism and nutrition disorders | ||||
Hyperkalaemia | 71/861 (8.2%) | 78/862 (9%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 42/861 (4.9%) | 48/862 (5.6%) | ||
Nervous system disorders | ||||
Headache | 22/861 (2.6%) | 45/862 (5.2%) | ||
Vascular disorders | ||||
Hypertension | 120/861 (13.9%) | 123/862 (14.3%) |
Limitations/Caveats
More Information
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 | Clinical Trial Information Desk |
---|---|
Organization | Akebia Therapeutics, Inc. |
Phone | +1 617-844-6128 |
trials@akebia.com |
- AKB-6548-CI-0015
- 2015-004774-14