Healthy
Conditions
Keywords
PER977, Ciraparantag, Whole Blood Clotting Time (WBCT), Rivaroxaban
Brief summary
This study is a randomized, single-blind, placebo-controlled study to assess the efficacy and safety of ciraparantag administered to healthy volunteers anticoagulated with rivaroxaban measuring clotting times using Whole Blood Clotting Time (WBCT).
Detailed description
This is a randomized, single-blind, placebo-controlled assessment of the efficacy and safety of ciraparantag administered to healthy volunteers measuring clotting times using WBCT as determined by the manual testing method. All subjects will undergo screening up to 36 days prior to enrollment. All enrolled subjects are to receive a single dose of 20 mg rivaroxaban in the morning on Days 1-3. On Day 3 (3.75 hours post rivaroxaban), subjects who have a minimum increase in clotting time of 25% (as measured by WBCT) are randomized and will receive a single IV dose 4 hours after the rivaroxaban dose, followed by serial testing of manual WBCT. Subjects are enrolled sequentially in up to 4 ciraparantag dose cohorts. There will be a safety review after completion of treatment in one cohort and prior to initiation of treatment in the subsequent cohort.
Interventions
DRUGCiraparantag
Ciraparantag (administered over 10 minutes)
DRUGPlacebo
Saline for injection
DRUGRivaroxaban
Rivaroxaban 20 mg given once per day (QD) in the morning
Sponsors
Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
General Inclusion Criteria: 1. Adults age 50 to 75 years 2. Laboratory tests (chemistry, hematology and coagulation assessments) and urinalysis performed during screening up to 36 days prior to administration of study treatment deemed not clinically significant by the principal investigator. 3. No clinically significant findings on 12-lead electrocardiogram (ECG) performed during screening 4. Body mass index (BMI) 18 to ≤ 32 kg/m2, inclusive 5. Male subjects agree to use appropriate contraception in addition to their partner using an acceptable form of contraception, when engaging in sexual activity during the course of the study. Moreover, male subjects should not donate sperm or attempt to impregnate a partner during the course of the study and for a period of 12 weeks following discharge from the study. 6. Female subjects must have a negative urine pregnancy test at screening AND: be surgically sterile OR postmenopausal for the last three months, OR in a monogamous relation with a male partner who has undergone a documented vasectomy a minimum of 6 months prior to study commencement. All females must agree to continue to use their method of birth control for the duration of the study and for a minimum of one complete menstrual cycle or 28 days following discharge from the study 7. Subjects who have participated in a prior study of ciraparantag must have been discharged from the study a minimum of 1 month prior to the planned treatment. 8. Subjects must understand and agree to comply with the requirements of the study and they must be willing to sign the informed consent form indicating voluntary consent to participate in the study prior to initiation of screening or study-related activities General
Exclusion criteria
1. History of major bleeding or clotting disorder 2. Females with a history of dysfunctional uterine bleeding 3. Smokers or use of tobacco and/or nicotine containing products within 3 months prior to dosing as determined by the subject's verbal history 4. Pregnant or breast-feeding 5. Males with a history of hormone therapy within 3 months prior to screening 6. Taking any type of chronic medication (including vitamin, nutritional and herbal supplements) for more than 14 consecutive days within the 4 weeks prior to study entry (use of hormonal contraceptives is acceptable) 7. Positive serologic test for human immunodeficiency virus (HIV), Hepatitis C virus antibody (HCV-Ab), or Hepatitis B surface antigen (HBsAg) 8. Donation of blood or blood products within 56 days prior to screening 9. Participation in any study with an investigational compound or device within 30 days prior to signing informed consent 10. Active drug or alcohol dependence within the prior 12 months or any condition that, in the opinion of the Investigator, would interfere with adherence to study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Achieving Complete Reversal of Anticoagulation (WBCT is ≤ 110% of Baseline) | Within 1 Hour | Complete reversal is achieved if WBCT (manual method) is ≤ 110% of baseline at any post-baseline time point up to and including 1 hour following ciraparantag/placebo administration) |
| Subjects Achieving Complete and Sustained Reversal of Anticoagulation (WBCT is ≤115%of Baseline) | Between 1 and 8 Hours | Complete and sustained reversal of anticoagulation is achieved for a subject if WBCT (manual method) is ≤ 115% of baseline at all time points between 1 and 8 hours (inclusive) following ciraparantag/placebo administration. |
Countries
United States
Participant flow
Recruitment details
One study site in the US enrolled subjects between May 2017 and November 2019
Pre-assignment details
69 subjects enrolled; 64 subjects were randomized and 5 subjects were not randomized. Of the 5 subjects not randomized, 2 did not achieve a sufficient level of anticoagulation per protocol, 1 was withdrawn by Investigator decision (due to an asymptomatic low heart rate), 1 subject withdrew consent, and 1 had an AE during the rivaroxaban administration period causing discontinuation (T wave inversion observed on ECG).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Subjects received 20 mg rivaroxaban once daily in the morning on Days 1-3. On Day 3, approximately 4 hours after last rivaroxaban dose, a single IV dose of saline for injection (placebo) was administered. | 16 |
| Ciraparantag 30 mg Subjects received 20 mg rivaroxaban once daily in the morning on Days 1-3. On Day 3, approximately 4 hours after last rivaroxaban dose, a single IV dose of 30 mg ciraparantag was administered. | 12 |
| Ciraparantag 60 mg Subjects received 20 mg rivaroxaban once daily in the morning on Days 1-3. On Day 3, approximately 4 hours after last rivaroxaban dose, a single IV dose of 60 mg ciraparantag was administered. | 12 |
| Ciraparantag 120 mg Subjects received 20 mg rivaroxaban once daily in the morning on Days 1-3. On Day 3, approximately 4 hours after last rivaroxaban dose, a single IV dose of 120 mg ciraparantag was administered. | 12 |
| Ciraparantag 180 mg Subjects received 20 mg rivaroxaban once daily in the morning on Days 1-3. On Day 3, approximately 4 hours after last rivaroxaban dose, a single IV dose of 180 mg ciraparantag was administered. | 12 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Ciraparantag 30 mg | Ciraparantag 60 mg | Ciraparantag 120 mg | Ciraparantag 180 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 3.89 | 57.8 years STANDARD_DEVIATION 5.67 | 56.1 years STANDARD_DEVIATION 6.73 | 53.8 years STANDARD_DEVIATION 3.1 | 55.9 years STANDARD_DEVIATION 4.89 | 55.5 years STANDARD_DEVIATION 5 |
| Baseline Whole Blood Clotting Time (WBCT, manual method) | 7.8 minutes STANDARD_DEVIATION 0.36 | 8.1 minutes STANDARD_DEVIATION 0.42 | 7.8 minutes STANDARD_DEVIATION 0.25 | 7.8 minutes STANDARD_DEVIATION 0.33 | 7.9 minutes STANDARD_DEVIATION 0.36 | 7.9 minutes STANDARD_DEVIATION 0.34 |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 6 Participants | 6 Participants | 5 Participants | 5 Participants | 30 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 6 Participants | 6 Participants | 7 Participants | 5 Participants | 32 Participants |
| Region of Enrollment United States | 16 Participants | 12 Participants | 12 Participants | 12 Participants | 12 Participants | 64 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 2 Participants | 0 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 14 Participants | 10 Participants | 10 Participants | 12 Participants | 9 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 5 |
| other Total, other adverse events | 3 / 16 | 0 / 12 | 2 / 12 | 8 / 12 | 10 / 12 | 1 / 5 |
| serious Total, serious adverse events | 0 / 16 | 0 / 12 | 0 / 12 | 0 / 12 | 1 / 12 | 0 / 5 |
Outcome results
Primary
Subjects Achieving Complete and Sustained Reversal of Anticoagulation (WBCT is ≤115%of Baseline)
Complete and sustained reversal of anticoagulation is achieved for a subject if WBCT (manual method) is ≤ 115% of baseline at all time points between 1 and 8 hours (inclusive) following ciraparantag/placebo administration.
Time frame: Between 1 and 8 Hours
Population: Pharmacodynamic population: all subjects who receive administration of study drug and provide at least one on-treatment whole blood clotting time measurement without protocol deviations with potential to affect these measurements.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Subjects Achieving Complete and Sustained Reversal of Anticoagulation (WBCT is ≤115%of Baseline) | 3 Participants |
| Ciraparantag 30 mg | Subjects Achieving Complete and Sustained Reversal of Anticoagulation (WBCT is ≤115%of Baseline) | 8 Participants |
| Ciraparantag 60 mg | Subjects Achieving Complete and Sustained Reversal of Anticoagulation (WBCT is ≤115%of Baseline) | 11 Participants |
| Ciraparantag 120 mg | Subjects Achieving Complete and Sustained Reversal of Anticoagulation (WBCT is ≤115%of Baseline) | 11 Participants |
| Ciraparantag 180 mg | Subjects Achieving Complete and Sustained Reversal of Anticoagulation (WBCT is ≤115%of Baseline) | 12 Participants |
Primary
Subjects Achieving Complete Reversal of Anticoagulation (WBCT is ≤ 110% of Baseline)
Complete reversal is achieved if WBCT (manual method) is ≤ 110% of baseline at any post-baseline time point up to and including 1 hour following ciraparantag/placebo administration)
Time frame: Within 1 Hour
Population: Pharmacodynamic population: all subjects who receive administration of study drug and provide at least one on-treatment whole blood clotting time measurement without protocol deviations with potential to affect these measurements.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Subjects Achieving Complete Reversal of Anticoagulation (WBCT is ≤ 110% of Baseline) | 3 Participants |
| Ciraparantag 30 mg | Subjects Achieving Complete Reversal of Anticoagulation (WBCT is ≤ 110% of Baseline) | 7 Participants |
| Ciraparantag 60 mg | Subjects Achieving Complete Reversal of Anticoagulation (WBCT is ≤ 110% of Baseline) | 11 Participants |
| Ciraparantag 120 mg | Subjects Achieving Complete Reversal of Anticoagulation (WBCT is ≤ 110% of Baseline) | 11 Participants |
| Ciraparantag 180 mg | Subjects Achieving Complete Reversal of Anticoagulation (WBCT is ≤ 110% of Baseline) | 12 Participants |