Secondary Hyperparathyroidism, Chronic Kidney Disease Clinical Trial
Official title:
A Multicenter Single-arm Extension Study to Characterize the Long-term Safety of Cinacalcet Hydrochloride in the Treatment of Secondary Hyperparathyroidism in Pediatric Subjects With Chronic Kidney Disease on Dialysis
| Verified date | June 2020 |
| Source | Amgen |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The primary objective of this study was to characterize the long-term safety and tolerability of cinacalcet in pediatric patients with chronic kidney disease (CKD) receiving dialysis.
| Status | Completed |
| Enrollment | 28 |
| Est. completion date | March 15, 2017 |
| Est. primary completion date | March 15, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 18 Years |
| Eligibility |
INCLUSION CRITERIA: All subjects: - Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any Study 20140159 activities/procedures being initiated. - Dialysate calcium concentration = 2.5 mEq/L at day 1 All subjects with > 14 days between the last study visit in Study 20130356 or Study 20110100 and screening for Study 20140159: - Subjects on anti-convulsant medication must be on a stable dose All subjects from 20130356: - Completed treatment through week 20 in the 20130356 study or on study at the time of Study 20130356 termination - Dry weight = 12.5 kg at day 1 of Study 20140159 Subjects Randomized to the 20130356 Standard of Care Arm Only: - intact parathyroid hormone (iPTH) value = 300 pg/mL (within 7 days of day 1 in Study 20140159) - Corrected calcium value = 8.8 mg/dL within 7 days of day 1 in Study 20140159 All Subjects from 20110100: - Completed week 26 End of Study visit in the, 20110100 study or on study at the time of Study 20110100 termination - Dry weight = 7 kg at day 1 of Study 20140159 EXCLUSION CRITERIA: General (studies 20130356 and 20110100): - Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s), other than Amgen Studies 20130356 or 20110100. - Other investigational procedures while participating in this study are excluded. - Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years. - Subject has known sensitivity to any of the products to be administered during dosing. - Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, electronic patient diary [ediary]) to the best of the subject and investigator's knowledge - History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion. - Subject previously has entered this study. - If sexually active, subject is not willing to use acceptable contraception during treatment and for at least 9 days after the end of treatment. - Subject is pregnant or breast feeding, or planning to become pregnant during the study or within 9 days after the end of treatment - History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrythmias, or other conditions associated with prolonged QT interval - A new onset of seizures or worsening of pre-existing seizure disorder All Subjects with > 14 days between the last study visit in Study 20130356 or Study 20110100 and the screening visit in Study 20140159 will have the following exclusion criteria applied during screening and day 1: - Unstable chronic heart failure defined as worsening pulmonary edema or other signs and symptoms as per investigator assessment during screening - Received therapy with commercial cinacalcet after the last study visit in Study 20130356 or Study 20110100 before day 1 of Study 20140159 - Scheduled date for kidney transplantation from a known living donor that makes completion of the study unlikely - Either new or recurrent cardiac ventricular arrhythmias requiring a change in treatment within 10 days prior to screening visit or day 1 of Study 20140159 screening - Hepatic impairment indicated by elevated levels of hepatic transaminase or bilirubin (aspartate aminotransferase [AST] = 1.5 × upper limit of normal [ULN] OR alanine aminotransferase [ALT] = 1.5 × ULN OR total bilirubin = 1 × ULN per institutional laboratory range) during screening All Subjects - Day 1 Study Visit: - Subject has an ongoing adverse event from Studies 20130356 or 20110100 that is considered related to investigational product and is = Common Terminology Criteria for Adverse Events (CTCAE) (v 4.0) grade 3, and/or considered clinically significant in the opinion of the investigator - Central laboratory values were not obtained/are not available at day 1 in Study 20140159 - Corrected QT Interval (QTc) > 500 ms, using Bazett's formula - QTc = 450 to = 500 ms, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist - Use of grapefruit juice, herbal medications, CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole), or CYP2D6 substrates (eg, flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine) - Use of concomitant medications that may prolong the QTc interval (eg, ondansetron, albuterol) |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | Research Site | Bruxelles | |
| Czechia | Research Site | Praha 5 | |
| France | Research Site | Paris | |
| Germany | Research Site | Hannover | |
| Germany | Research Site | Heidelberg | |
| Germany | Research Site | Marburg | |
| Greece | Research Site | Athens | |
| Hungary | Research Site | Szeged | |
| Italy | Research Site | Genova | |
| Poland | Research Site | Krakow | |
| Poland | Research Site | Lodz | |
| Russian Federation | Research Site | Moscow | |
| Russian Federation | Research Site | Saint Petersburg | |
| Russian Federation | Research Site | Samara | |
| Ukraine | Research Site | Kyiv | |
| United States | Research Site | Baltimore | Maryland |
| United States | Research Site | Boston | Massachusetts |
| United States | Research Site | Cincinnati | Ohio |
| United States | Research Site | Cleveland | Ohio |
| United States | Research Site | Columbus | Ohio |
| United States | Research Site | Dallas | Texas |
| United States | Research Site | Greenville | North Carolina |
| United States | Research Site | Houston | Texas |
| United States | Research Site | Jackson | Mississippi |
| United States | Research Site | Kansas City | Missouri |
| United States | Research Site | Los Angeles | California |
| United States | Research Site | Minneapolis | Minnesota |
| United States | Research Site | New York | New York |
| United States | Research Site | Oklahoma City | Oklahoma |
| United States | Research Site | Saint Louis | Missouri |
| United States | Research Site | Salt Lake City | Utah |
| United States | Research Site | Tucker | Georgia |
| United States | Research Site | West Orange | New Jersey |
| Lead Sponsor | Collaborator |
|---|---|
| Amgen |
United States, Belgium, Czechia, France, Germany, Greece, Hungary, Italy, Poland, Russian Federation, Ukraine,
Warady BA, Ng E, Bloss L, Mo M, Schaefer F, Bacchetta J. Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2020 May 4. doi: 10.1007/s00467-020-04516-4. [Epub ahead of print] — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events | Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE, v4.0). The investigator assessed whether the adverse event was possibly related to the study drug as indicated by a "yes" or "no" response to the question: Is there a reasonable possibility that the event may have been caused by the study drug? | From first dose of study drug in the extension study up to 4 weeks after the last dose; 32 weeks. | |
| Secondary | Percentage of Participants Achieving = 30% Reduction in iPTH From Baseline to Mean Value During Weeks 11 and 15 | This endpoint was analyzed in participants who received SOC only in parent study 20130356. Participants who had no iPTH values during weeks 11 or 15 were considered non-responders. Data collected more than 7 days after the last dose of study drug were excluded. |
Baseline (defined as the mean values of samples collected during the screening period and day 1 pre-dose in the extension study) and weeks 11 and 15 | |
| Secondary | Percentage of Participants Achieving = 30% Reduction in iPTH From Baseline to Mean Value During Weeks 23 and 28 | This endpoint was analyzed in participants who received SOC only in parent study 20130356. For participants who had no values during week 23 and 28, the mean of the last 2 available post-baseline values collected in the dose-titration phase was used. If only 1 post-baseline value was available, this single value was used. If no post-baseline value was available, the participant was considered a non-responder. Data collected more than 7 days after the last dose of study drug were excluded. |
Extension study baseline and weeks 23 and 28 | |
| Secondary | Percent Change From Baseline in iPTH to the Mean Value During Weeks 23 and 28 | This endpoint was analyzed in participants who received SOC only in parent study 20130356. For participants who had no values during week 23 and week 28, the mean of the last 2 available post-baseline values collected in the dose-titration phase was used. If only 1 post-baseline value was available, this single value was used. If no post-baseline value was available, the participant was excluded from the analysis. Data collected more than 7 days after the last dose of study drug were excluded. |
Extension study baseline and weeks 23 and 28 | |
| Secondary | Percentage of Participants Who Achieved Mean iPTH = 300 pg/mL During Weeks 23 and 28 | For participants who had no values during week 23 and 28, the mean of the last 2 available post-baseline values collected in the dose-titration phase was used. If only 1 post-baseline value was available, this single value was used. If no post-baseline value was available, the participant was considered a non-responder. Data collected more than 7 days after the last dose of study drug were excluded. | Weeks 23 and 28 | |
| Secondary | Change From Baseline in Corrected Serum Calcium to the Mean Value During Weeks 23 to 28 | For participants who had no values during weeks 23 to 28, the mean of the last 2 available post-baseline values collected in the dose-titration phase was used. If only 1 post-baseline value was available, this single value was used. If no post-baseline value was available, the participant was excluded from the analysis. Data collected more than 7 days after the last dose of study drug were excluded. | Extension study baseline and weeks 23 and 28 | |
| Secondary | Change From Baseline in Serum Phosphorus to the Mean Value During Weeks 23 to 28 | For participants who had no values during weeks 23 to 28, the mean of the last 2 available post-baseline values collected in the dose-titration phase was used. If only 1 post-baseline value was available, this single value was used. If no post-baseline value was available, the participant was excluded from the analysis. Data collected more than 7 days after the last dose of study drug were excluded. | Extension study baseline and weeks 23 and 28 | |
| Secondary | Serum Corrected Calcium at Baseline, Week 11, and Week 28 | Data collected more than 7 days after the last dose of study drug were excluded. | Extension study baseline, week 11 and week 28 | |
| Secondary | Serum Phosphorus at Baseline, Week 11, and Week 28 | Data collected more than 7 days after the last dose of study drug were excluded. | Extension study baseline, week 11 and week 28 | |
| Secondary | Percentage of Participants Achieving = 30% Reduction in iPTH From Day 1 of Cinacalcet Treatment to Mean Value During Weeks 11 and 15 | The percentage of participants who achieved = 30% reduction in iPTH measured from the date the initial dose of cinacalcet was administered, in parent study 20130356 or 20110100 for participants who received cinacalcet in the parent study, or in the extension study for participants who received SOC only in parent study 20130356. Participants who had no iPTH values during weeks 11 and 15 were considered non-responders. Data collected more than 7 days after the last dose of study drug were excluded. |
Baseline and weeks 11 and 15, relative to day 1 of cinacalcet treatment. | |
| Secondary | Percentage of Participants Achieving = 30% Reduction in iPTH From Day 1 of Cinacalcet Treatment to Mean Value During Weeks 23 and 28 | The percentage of participants who achieved = 30% reduction in iPTH measured from the date the initial dose of cinacalcet was administered, in parent study 20130356 or 20110100 for participants who received cinacalcet in the parent study, or in the extension study for participants who received SOC only in parent study 20130356. For participants who did not have an iPTH value during weeks 23 and 28, the mean of the last two available post-baseline values collected at protocol-specified visits was used. If only one post-baseline value was available, this single value was used. If no post-baseline value was available, the participant was considered a non-responder. Data collected more than 7 days after the last dose of study drug were excluded. |
Baseline and weeks 23 and 28, relative to day 1 of cinacalcet treatment. | |
| Secondary | Percent Change From Day 1 of Cinacalcet Treatment in iPTH Over Time | Percent change in iPTH measured from the date the initial dose of cinacalcet was administered, either in parent study 20130356 or 20110100, or in the extension study for participants who received SOC only in parent study 20130356. Data collected more than 7 days after the last dose of study drug were excluded. |
Baseline and weeks 3, 7, 11, 15, 17, 18, 19, 20, 23, 27, 31, 35, 39, 43, 48, 52, relative to day 1 of cinacalcet treatment, and at the end of treatment visit and end of study visit (4 weeks after the end of treatment visit). | |
| Secondary | Change From Day 1 of Cinacalcet Treatment in Serum Corrected Calcium Over Time | Change in corrected calcium measured from the date the initial dose of cinacalcet was administered, either in parent study 20130356 or 20110100, or in the extension study for participants who received SOC only in parent study 20130356. Data collected more than 7 days after the last dose of study drug were excluded. |
Baseline and weeks 3, 7, 11, 15, 17, 18, 19, 20, 23, 27, 31, 35, 39, 43, 48, 52, relative to day 1 of cinacalcet treatment, and at the end of treatment visit and end of study visit (4 weeks after the end of treatment visit). | |
| Secondary | Change From Day 1 of Cinacalcet Treatment in Serum Phosphorus Over Time | Change in phosphorus measured from the date the initial dose of cinacalcet was administered, either in parent study 20130356 or 20110100, or in the extension study for participants who received SOC only in parent study 20130356. Data collected more than 7 days after the last dose of study drug were excluded. |
Baseline and weeks 3, 7, 11, 15, 17, 18, 19, 20, 23, 27, 31, 35, 39, 43, 48, 52, relative to day 1 of cinacalcet treatment, and at the end of treatment visit and end of study visit (4 weeks after the end of treatment visit). |