Doptelet Drug Information
Generic name: AVATROMBOPAG
Uses of Doptelet
Treatment of Thrombocytopenia in Patients with Chronic Liver Disease (CLD)
DOPTELET is indicated for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure.
Treatment of Thrombocytopenia in Adult Patients with Chronic Immune Thrombocytopenia (ITP)
DOPTELET is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.
Treatment of Thrombocytopenia in Pediatric Patients 1 Year and Older with Persistent
or Chronic Immune Thrombocytopenia (ITP) DOPTELET is indicated for the treatment of thrombocytopenia in pediatric patients 1 year and older with persistent or chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.
Dosage & Administration of Doptelet
| Less than 40×109/L | 60 mg (3 tablets) orally once daily |
|---|---|
| 40×109/L to less than 50×109/L | 40 mg (2 tablets) orally once daily |
Side Effects of Doptelet
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients with Chronic Liver Disease The safety of DOPTELET was evaluated in two international, identically designed, randomized, double-blind, placebo-controlled trials, ADAPT-1 and ADAPT-2, in which 430 patients with chronic liver disease and thrombocytopenia received either DOPTELET (n=274) or placebo (n=156) daily for 5 days prior to a scheduled procedure, and had 1 post-dose safety assessment. Patients were divided into two groups based on their mean platelet count at baseline: Low Baseline Platelet Count Cohort (less than 40×10 9 /L) who received DOPTELET 60 mg once daily for 5 days High Baseline Platelet Count Cohort (40 to less than 50×10 9 /L) who received DOPTELET 40 mg once daily for 5 days The majority of patients were males (65%) and median subject age was 58 years (ranging from 19-86 years of age). The racial and ethnic distribution was White (60%), Asian (33%), Black (3%) and Other (3%). The most common adverse reactions (those occurring in ≥3% of patients) in the DOPTELET-treated groups (60 mg or 40 mg) across the pooled data from the two trials are summarized in Table 8. Table 8 : Adverse Reactions with a Frequency ≥3% in Patients with C hronic L iver D isease Treated with DOPTELET – Pooled Data ADAPT-1 and ADAPT-2 Adverse Reactions Low Baseline Platelet Count Cohort (˂40 × 10 9 /L) High Baseline Platelet Count Cohort (≥40 to ˂50 × 10 9 /L) Combined Baseline Platelet Count Cohort s (˂ 5 0 × 10 9 /L) DOPTELET 60 mg (N=159) % Placebo (N=91) % DOPTELET 40 mg (N=115) % Placebo (N=65) % Total DOPTELET (N=274) % Total Placebo (N=156) % Pyrexia 11 9 8 9 10 9 Abdominal Pain 6 7 7 6 7 6 Nausea 6 8 7 6 7 7 Headache 4 8 7 5 6 6 Fatigue 4 4 3 2 4 3 Edema Peripheral 3 2 4 2 3 2 For the Low Baseline Platelet Count Cohort, the incidence of serious adverse reactions was 7% (11/159) in the 60 mg DOPTELET treatment group.
For the High Baseline Platelet Count Cohort, the incidence of serious adverse reactions was 8% (9/115) in the 40 mg DOPTELET treatment group. The most common serious adverse reaction reported with DOPTELET was hyponatremia. Two DOPTELET-treated patients (0.7%) developed hyponatremia.
Adverse reactions resulting in discontinuation of DOPTELET were anemia, pyrexia, and myalgia; each was reported in a single (0.4%) patient in the DOPTELET (60 mg) treatment group. Adult Patients with Chronic Immune Thrombocytopenia The safety of DOPTELET was evaluated in four clinical trials in adult patients with chronic immune thrombocytopenia: two Phase 3 trials (one randomized, double-blind, placebo-controlled trial, and one randomized, double-blind, active-controlled trial) and two Phase 2 trials (one randomized, double-blind, placebo-controlled, dose-ranging, trial, and one open-label extension trial) in 161 patients with chronic immune thrombocytopenia in both the double-blind and open-label extension phases. The pooled safety data from these four clinical trials includes 128 patients who received 2.5 to 40 mg of DOPTELET once daily for a median duration of exposure of 29.1 weeks and had 1 post-dose safety assessment.
The majority of patients were female (63%) and median subject age was 50.5 years (ranging from 18-88 years of age). The racial and ethnic distribution was White (84%), Black (6%), Asian (6%) and Other (6%). The most common adverse reactions (those occurring in ≥10% of patients) in the DOPTELET-treated patients across the pooled safety data from the four trials are summarized in Table 9. Table 9 : Adverse Reactions with a Frequency ≥10% in Adult Patients with Chronic Immune Thrombocytopenia Treated with DOPTELET – Pooled Data from Clinical Trials Adverse Reactions DOPTELET (N=128) % Placebo (N= 22) % Headache 31 14 Fatigue 28 9 Contusion 26 18 Epistaxis 19 18 Upper Respiratory Tract Infection 15 5 Arthralgia 13 0 Gingival Bleeding 13 0 Petechiae 11 9 Nasopharyngitis 10 0 The incidence of serious adverse reactions was 9% (12/128) in the DOPTELET treatment group. Serious adverse reactions reported in more than 1 individual DOPTELET-treated patient included headache, occurring in 1.6% (2/128). Adverse reactions resulting in discontinuation of DOPTELET that were reported in more than 1 patient included headache, occurring in 1.6% (2/128). Pediatric Patients with Persistent or Chronic Immune Thrombocytopenia The data described below reflect median exposure to DOPTELET of 12 weeks for 54 pediatric patients (≥1 to <18 years of age) with persistent or chronic immune thrombocytopenia across the core phase of one double-blind, placebo-controlled trial . Table 10 presents the most common adverse reactions (experienced by greater than or equal to 10% of pediatric patients 1 year and older receiving DOPTELET) with a higher incidence for DOPTELET versus placebo. Table 10: Adverse Reactions in Pediatric Patients with Persistent or Chronic Immune Thrombocytopenia Treated with DOPTELET a Adverse Reactions DOPTELET (N=54) % Placebo (N=21) % Viral Infection b 20 5 Nasopharyngitis 20 10 Cough 17 0 Pyrexia 17 0 Oropharyngeal Pain 13 0 a Adverse reactions that occurred in ≥10% of DOPTELET-treated patients and ≥2% more than placebo-treated patients. b Viral infection includes viral upper respiratory infection, viral infection, COVID-19, parainfluenza virus infection, and rhinovirus infection.
Two patients experienced serious adverse reactions: thrombocytosis and headache. Two patients experienced adverse reactions resulting in discontinuation of DOPTELET: vomiting and headache (in one patient) and leukocytosis (in one patient).
Postmarketing Experience
The following adverse reactions have been identified during post approval use of DOPTELET. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune System Disorders : Hypersensitivity reactions including pruritus, rash, choking sensation, erythema, pharyngeal edema, pruritus generalized, rash macular, swelling face, and swollen tongue.
Warnings & Cautions for Doptelet
Thrombotic/Thromboembolic Complications
DOPTELET is a thrombopoietin (TPO) receptor agonist and TPO receptor agonists have been associated with thrombotic and thromboembolic complications in patients with chronic liver disease or immune thrombocytopenia. In patients with chronic liver disease, thromboembolic events (portal vein thrombosis) occurred in 0.4% (1/274) of patients receiving DOPTELET. In adult patients with chronic immune thrombocytopenia, thromboembolic events (arterial or venous) occurred in 7% (9/128) of patients receiving DOPTELET. Consider the potential increased thrombotic risk when administering DOPTELET to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions (e.g., Factor V Leiden, Prothrombin 20210A, Antithrombin deficiency or Protein C or S deficiency) and acquired risk factors (e.g., antiphospholipid syndrome). DOPTELET should not be administered to patients with chronic liver disease or immune thrombocytopenia in an attempt to normalize platelet counts. Monitor platelet counts and follow the dosing guidelines to achieve target platelet counts . Monitor patients receiving DOPTELET for signs and symptoms of thromboembolic events and institute treatment promptly.
Drug Interactions with Doptelet
Effect of Other Drugs on
DOPTELET in Patients with Persistent or Chronic Immune Thrombocytopenia Moderate or Strong Dual Inhibitors of CYP2C9 and CYP3A4 Concomitant use with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4 increases avatrombopag AUC , which may increase the risk of DOPTELET toxicities. Reduce the starting dosage of DOPTELET when used concomitantly with a moderate or strong dual inhibitor of CYP2C9 and CYP3A4 (see Table 4 and Table 7) . In patients starting moderate or strong dual inhibitors of CYP2C9 and CYP3A4 while receiving DOPTELET, monitor platelet counts and adjust DOPTELET dose as necessary (see Table 2 and Table 3; and Table 5 and Table 6) . Moderate or Strong Dual Inducers of CYP2C9 and CYP3A4 Concomitant use with a moderate or strong dual inducer of CYP2C9 and CYP3A4 decreases avatrombopag AUC , which may reduce DOPTELET efficacy. Increase the recommended starting dosage of DOPTELET when used concomitantly with a moderate or strong dual inducer of CYP2C9 and CYP3A4 (see Table 4 and Table 7) . In patients starting moderate or strong dual inducers of CYP2C9 and CYP3A4 while receiving DOPTELET, monitor platelet counts and adjust DOPTELET dose as necessary (see Table 2 and Table 3; and Table 5 and Table 6) . Patients with Chronic Liver Disease No dosage adjustments are required for patients with chronic liver disease.
Pregnancy Safety for Doptelet
Pregnancy Risk Summary Based on findings from animal reproduction studies, DOPTELET may cause fetal harm when administered to a pregnant woman ( see Data ). The available data on DOPTELET in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, oral administration of avatrombopag resulted in adverse developmental outcomes when administered during organogenesis in rabbits and during organogenesis and the lactation period in rats. However, these findings were observed at exposures based on an AUC substantially higher than the AUC observed in patients at the maximum recommended dose of 60 mg once daily.
Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In embryo-fetal development studies, avatrombopag was administered during organogenesis at doses of 100, 300, and 1000 mg/kg/day in rats and doses of 100, 300, and 600 mg/kg/day in rabbits. Minimal decreases in fetal weights were observed in rats at the maternally toxic dose of 1000 mg/kg/day with exposures 190 times the human exposure based on AUC. Spontaneous abortions were observed at all doses tested in rabbits and were associated with decreased body weights and food consumption at 300 and 600 mg/kg/day; exposures at the lowest dose of 100 mg/kg/day were 10 times the AUC in patients at the maximum recommended dose of 60 mg once daily.
There were no embryo-fetal effects in rats administered avatrombopag at doses up to 100 mg/kg/day (53 times the human exposure based on AUC) or rabbits administered avatrombopag at doses up to 600 mg/kg (35 times the human exposure based on AUC). In pre- and postnatal development studies in rats, avatrombopag was administered during both the organogenesis and lactation periods at doses ranging from 5 to 600 mg/kg/day. Doses of 100, 300, and 600 mg/kg/day caused maternal toxicity leading to total litter losses, decreased body weight in pups, and increased pup mortality, with the majority of the pup mortality occurring from postnatal days 14 to 21. At a dose of 50 mg/kg/day that did not produce clear maternal toxicity, avatrombopag caused increased pup mortality from postnatal days 4 to 21, and mortality continued through postnatal day 25. The 50 mg/kg/day dose also decreased body weight gain in the pups, resulting in a delay in sexual maturation. There were no effects on behavioral or reproductive functions in the offspring.
The 50 mg/kg/day dose resulted in maternal exposures 43 times and pup exposures approximately 3 times the AUC observed in patients at the maximum recommended dose of 60 mg once daily.
Pediatric Use of Doptelet
Pediatric Use The safety and effectiveness of DOPTELET tablet for the treatment of persistent or chronic ITP have been established in pediatric patients aged 6 years and older. The safety and effectiveness of DOPTELET SPRINKLE for the treatment of persistent or chronic ITP have been established in pediatric patients aged 1 to <6 years. Use of DOPTELET tablet and DOPTELET SPRINKLE for their respective populations is supported by evidence from an adequate and well-controlled study in pediatric patients aged 1 year and older . Juvenile Animal Toxicity Data In a 10-week juvenile toxicology study in rats, avatrombopag was administered at doses ranging from 20 to 300 mg/kg/day.
There was no test article-related mortality and there were no clinical signs at doses up to 300 mg/kg/day. In the stomach, dose-dependent degeneration, regenerative hyperplasia, and atrophy of the glandular epithelium occurred at 100 and 300 mg/kg/day; exposures at 100 mg/kg/day in male rats were 14 times the AUC in patients at the highest recommended dose of 60 mg once daily. An increased incidence of background focal mineralization was also observed in the kidneys of females at 300 mg/kg/day (female rat exposure was 50 times the human exposure based on AUC at the 60 mg daily dose).
Overdosage Information for Doptelet
In the event of overdose, platelet count may increase excessively and result in thrombotic or thromboembolic complications. Closely monitor the patient and platelet count. Treat thrombotic complications in accordance with standard of care.
No antidote for DOPTELET overdose is known. Hemodialysis is not expected to enhance the elimination of DOPTELET because avatrombopag is only approximately 6% renally excreted and is highly bound to plasma proteins. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Clinical Studies of Doptelet
Patients with Chronic Liver Disease
The efficacy of DOPTELET for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a procedure was established in 2 identically-designed multicenter, randomized, double-blind, placebo-controlled trials (ADAPT-1 and ADAPT-2 ). In each trial, patients were assigned to the Low Baseline Platelet Count Cohort (<40×10] and ADAPT-2 ). In each trial, patients were assigned to the Low Baseline Platelet Count Cohort (<40×10 9 /L) or the High Baseline Platelet Count Cohort (≥40 to <50×10 9 /L) based on their platelet count at baseline. Patients were then randomized in a 2:1 ratio to either DOPTELET or placebo. Patients were stratified according to hepatocellular cancer (HCC) status and risk of bleeding associated with the elective procedure (low, moderate, or high). Patients undergoing neurosurgical interventions, thoracotomy, laparotomy or organ resection were not eligible for enrollment.
Patients in the Low Baseline Platelet Count Cohort received 60 mg DOPTELET or matching placebo once daily for 5 days, and patients in the High Baseline Platelet Count Cohort received 40 mg DOPTELET or matching placebo once daily for 5 days. Eligible patients were scheduled to undergo their procedure (low, moderate, or high bleeding risk) 5 to 8 days after their last dose of treatment. Patient populations were similar between the pooled Low and High Baseline Platelet Count Cohorts and consisted of 66% male and 35% female; median age 58 years and 61% White, 34% Asian, and 3% Black.
In ADAPT-1, a total of 231 patients were randomized, 149 patients were treated with DOPTELET and 82 patients were treated with placebo. In the Low Baseline Platelet Count Cohort, the mean baseline platelet count for the DOPTELET-treated group was 31.1×10 9 /L and for the placebo-treated patients was 30.7×10 9 /L. In the High Baseline Platelet Count Cohort, the mean baseline platelet count for the DOPTELET-treated patients was 44.3×10 9 /L and for placebo-treated patients was 44.9×10 9 /L. In ADAPT-2, a total of 204 patients were randomized, 128 patients were treated with DOPTELET and 76 patients were treated with placebo. In the Low Baseline Platelet Count Cohort, the mean baseline platelet count for the DOPTELET-treated group was 32.7×10 9 /L and for the placebo-treated patients was 32.5×10 9 /L. In the High Baseline Platelet Count Cohort, the mean baseline platelet count for the DOPTELET-treated patients was 44.3×10 9 /L and for the placebo-treated patients was 44.5×10 9 /L. Across both baseline platelet count cohorts and the avatrombopag and placebo treatment groups, patients underwent a broad spectrum of types of scheduled procedures that ranged from low to high bleeding risk.
Overall, the majority of patients (60.8% subjects) in all treatment groups underwent low bleeding risk procedures, 17.2% (70/430) of patients underwent procedures associated with moderate bleeding risk, and 22.1% (90/430) of subjects underwent procedures associated with high bleeding risk. The proportions of patients undergoing low, moderate, and high-risk procedures were similar between the avatrombopag and placebo treatment groups. The major efficacy outcome was the proportion of patients who did not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following an elective procedure.
Additional secondary efficacy outcomes were the proportion of patients who achieved platelet counts of >50×10 9 /L on the day of procedure, and the change in platelet count from baseline to procedure day. Responders were defined as patients who did not require a platelet transfusion or any rescue procedure for bleeding after randomization and up to 7 days following a scheduled procedure. The following were considered rescue therapies to manage the risk of bleeding associated with a procedure: whole blood transfusion, packed red blood cell (RBC) transfusion, platelet transfusion, fresh frozen plasma (FFP) or cryoprecipitate administration, Vitamin K, desmopressin, recombinant activated factor VII, aminocaproic acid, tranexamic acid, or surgical or interventional radiology procedures performed to achieve hemostasis and control blood loss.
In both baseline platelet count cohorts, patients in the DOPTELET treatment groups had a greater proportion of responders than the corresponding placebo treatment groups that was both clinically meaningful and statistically significant as detailed in Table 13. Table 13 : Proportion of Patients Not Requiring a Platelet Transfusion or Any Rescue Procedure for Bleeding by Baseline Platelet Count Cohort and Treatment Group – ADAPT-1 and ADAPT-2 Low Baseline Platelet Count Cohort (<40 × 10 9 /L) Category ADAPT-1 ADAPT-2 DOPTELET 60 mg (n=90) Placebo (n=48) DOPTELET 60 mg (n=70) Placebo (n=43) Responders 95% CI a 66% 23% 69% 35% Difference of Proportion vs. Placebo b 95% CI c 43% 34% p-value d ˂ 0.0001 0.0006 High Baseline Platelet Count Cohort (≥40 to <50 × 10 9 /L) Category ADAPT-1 ADAPT-2 DOPTELET 40 mg (n=59) Placebo (n= 34) DOPTELET 40 mg (n=58) Placebo (n=33) Responders 95% CI a 88% 38% 88% 33% Difference of Proportion vs. Placebo b 95% CI c 50% 55% p-value d ˂ 0.0001 ˂ 0.0001 Two-sided 95% confidence interval based on normal approximation.
Difference of Proportion vs. placebo = Proportion of Responders for DOPTELET – Proportion of Responders for placebo. 95% confidence interval calculated based on normal approximation. By Cohhran-Mantel-Haenszel Testing stratified by bleeding risk for the procedure. In addition, both trials demonstrated a higher proportion of patients who achieved the target platelet count of ≥50×10 9 /L on the day of procedure, a secondary efficacy endpoint, in both DOPTELET-treated groups versus the placebo-treated groups for both cohorts (Low Baseline Platelet Count Cohort – ADAPT-1: 69% vs 4%, respectively; p˂0.0001, ADAPT-2: 67% vs 7%, respectively; p <0.0001; High Baseline Platelet Count Cohort – ADAPT-1: 88% vs 21%, respectively; p <0.0001: ADAPT-2: 93% vs 39%, respectively; p <0.0001). Further, both trials demonstrated a greater mean change in platelet counts from baseline to the day of the procedure, a secondary efficacy endpoint, in both DOPTELET-treated groups versus the placebo-treated groups for both cohorts (Low Baseline Platelet Count Cohort – ADAPT-1: 32×10 9 /L vs 0.8×10 9 /L, respectively; p<0.0001; ADAPT-2: 31.3×10 9 /L vs 3.0×10 9 /L, respectively; p <0.0001; High Baseline Platelet Count Cohort – ADAPT-1: 37.1×10 9 /L vs 1.0×10 9 /L, respectively; p <0.0001; ADAPT-2: 44.9×10 9 /L vs 5.9×10 9 /L, respectively; p <0.0001). A measured increase in platelet counts was observed in both DOPTELET treatment groups over time beginning on Day 4 post-dose, that peaked on Day 10-13, decreased 7 days post-procedure, and then returned to near baseline values by Day 35.
Adult Patients with Chronic Immune Thrombocytopenia Randomized Phase 3 Clinical Trial
The efficacy of DOPTELET in adult patients with chronic immune thrombocytopenia was evaluated in a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial ( NCT01438840 ). Patients had previously received one or more prior chronic immune thrombocytopenia therapies and had an average of screening and baseline platelet counts <30×10 9 /L. Patients were centrally stratified by splenectomy status, baseline platelet count (≤15×10 9 /L or >15×10 9 /L to <30×10 9 /L), and use of concomitant chronic immune thrombocytopenia medication, and then randomized (2:1) to receive either DOPTELET or placebo for 6 months. Patients received a starting dose of 20 mg once daily, with doses subsequently titrated based on platelet response. Forty-nine patients were randomized, 32 to DOPTELET and 17 to placebo, with similar mean baseline platelet counts in the 2 treatment groups (14.1 ×10 9 /L and 12.7 ×10 9 /L, respectively). The median age was 44 years, 63% were female, and 94% were Caucasian, 4% Asian and 2% Black.
The median duration of exposure was 26 weeks for DOPTELET-treated patients and 6 weeks for placebo-treated patients. The major efficacy outcome in this trial was the cumulative number of weeks in which the platelet count was ≥50×10 9 /L during the 6-month treatment period in the absence of rescue therapy. DOPTELET-treated patients had a longer duration of platelet counts ≥50×10 9 /L in the absence of rescue therapy than those who received placebo (median 12.4 vs 0 weeks, respectively, p<0.0001) (see Table 14 ). Table 14 : Cumulative Number of Weeks of Platelet Response – Phase 3 Trial in Adult Patients with Chronic Immune Thrombocytopenia Primary Efficacy Analysis DOPTELET (n=32) Placebo (n=17) Cumulative Number of Weeks with a Platelet Response* Mean (SD) 12.0
Median 12.4 0.0 Min, Max 0, 25 0, 2 p-value of Wilcoxon
rank sum test <0.0001 Max=maximum, Min=minimum, SD=Standard deviation. *Cumulative number of weeks of platelet response is defined as the total numbers of weeks in which the platelet count was ≥50×10 9 /L during 6 months of treatment in the absence of rescue therapy. In addition, a larger proportion of patients in the DOPTELET treatment group had platelet counts ≥50×10 9 /L at Day 8 compared to placebo (21/32; 66% vs 0/17; 0.0%, respectively; p<0.0001).
Pediatric Patients with Persistent or Chronic Immune Thrombocytopenia
The efficacy and safety of DOPTELET was evaluated in pediatric patients ≥1 to <18 years of age with persistent or chronic immune thrombocytopenia in a randomized, double-blind, placebo-controlled trial (NCT 04516967), which included a 12-week randomized treatment phase (Core Phase). Patients were required to have had a diagnosis of primary ITP for ≥6 months and had an insufficient response to at least one previous treatment, with an average of 2 baseline platelet counts less than 30×10 9 /L. Patients (n=75) were randomized (3:1) to receive DOPTELET (n=54) or placebo (n=21). The starting dose for patients 6 years and older was 20 mg (tablet), while the starting dose for the youngest cohort was 10 mg (oral granules mixed with a soft food or liquid). Doses could be subsequently titrated based on platelet response. Enrollment was 52% male and 48% female. The median age of patients receiving DOPTELET was 8.5 years (range 1 to 17) while the median age of patients receiving placebo was 10.0 years (range 3 to 17). Patients identified their race as White (84%), Asian (5.3%), and Other (5.3%); 5.3% did not report race.
Patients identified their ethnicity as Not Hispanic or Latino (86.7%) and Hispanic or Latino (6.7%); 2.7% did not report ethnicity and 4% had unknown ethnicity. The median baseline platelet counts were 10.4×10 9 /L in the DOPTELET group and 11.5×10 9 /L in the placebo group. The percentage of patients who had received 3 or more prior ITP therapies was 68.5% in the avatrombopag group and 66.7% in the placebo group.
Most patients in the trial received at least one other TPO receptor agonist as a prior therapy (74.1% in the DOPTELET group and 71.4% in the placebo group). The efficacy of DOPTELET in this trial was evaluated by durable platelet response, defined as the proportion of patients achieving at least 6 out of 8 weekly platelet counts ≥50×10 9 /L during the last 8 weeks of the 12-week Treatment Period in the Core Phase in the absence of rescue medication ( Table 15 ). Efficacy was also evaluated by platelet response, defined as the proportion of subjects achieving at least 2 consecutive platelet assessments ≥50×10 9 /L in the Core Phase in the absence of rescue medication. Table 15: Durable Platelet Response and Platelet Response - Phase 3 Trial in Pediatric Patients with Persistent or Chronic ITP - Full Analysis Set Endpoint DOPTELET (N=54) Placebo (N=21) Durable platelet response, n% Yes 15 0 No 39 21 Difference of proportion (avatrombopag – placebo) (95% CI)
CMH (avatrombopag vs. placebo) p-value p=0.0077 a Platelet response, n% Yes 44
0 No 10 21 Difference of proportion (avatrombopag – placebo) (95% CI)
CMH (avatrombopag vs. placebo) p-value p <0.0001 a CI, Confidence interval;
CMH, Cochran-Mantel-Haenszel; N, Total number of subjects; n, Number of subjects; Full Analysis Set includes all randomized subjects. a Denotes p-value from Fisher’s Exact Test, which was used in place of CMH test due to sparse number of responders in the strata. Note: The CMH test is adjusted for age cohort and baseline platelet counts. DOPTELET was superior to placebo in other major efficacy outcomes that evaluated platelet counts.
At Day 8, 55.6% (95% CI: 41.4%, 69.1%) of DOPTELET versus no placebo patients (95% CI: 0.0%, 16.1%) had a platelet count ≥50×10 9 /L in the absence of rescue therapy (p <0.0001). The mean percentage of weeks that subjects had a platelet count ≥50×10 9 /L during the Core Phase in the absence of rescue therapy was significantly higher for DOPTELET versus placebo, 48.9% (SD: 25.22%) versus 1.2% (SD: 3.92%) (p <0.0001). The proportion of subjects who required rescue therapy during the Core Phase was significantly lower (p=0.0008) in the DOPTELET group (7.4% ) than in the placebo group (42.9% ).
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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