Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
JNJ-70033093 · 5 trials · 2 indications
Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death.
Plasma concentration of JNJ-70033093 after single dose administration will be analyzed.
Observed plasma concentration of JNJ-70033093 after multiple dose administration will be analyzed.
Cmax is defined as maximum observed plasma concentration after administration of JNJ-70033093.
AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to time of last quantifiable concentration after administration of JNJ-70033093.
AUC (0-inf) is defined as area under the plasma concentration-time curve from time 0 to infinity after administration of JNJ-70033093.
Tmax is defined time to reach the maximum observed plasma concentration.
Apparent elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve.
Cmax is the maximum observed analyte concentration.
Tmax is the actual sampling time to reach the maximum observed analyte concentration
AUC(0-12h) is the area under the time-concentration curve (AUC) from time 0 (dosing time) to 12 hours before steady state.
T(1/2) is the apparent terminal elimination half-life is the time measured for the analyte concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Cmax is the maximum observed analyte concentration.
AUC (0-last) is area under the analyte concentration-time curve (AUC) from time 0 to time of the last quantifiable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.
Cmax is the maximum observed plasma concentration. Cmax geometric mean ratio of Treatment C (JNJ-70033093 + digoxin) relative to Treatment A (JNJ-70033093) will be reported to assess the effect of digoxin on the pharmacokinetics (PK) of JNJ-70033093.
Cmax is the maximum observed plasma concentration. Cmax geometric mean ratio of Treatment C (JNJ-70033093 + Digoxin) relative to Treatment B (digoxin) will be reported to assess the effect of JNJ-70033093 on the PK of digoxin.
AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose. AUC (0-24) geometric mean ratio of Treatment C (JNJ-70033093 + digoxin) relative to Treatment A (JNJ-70033093) will be reported to assess the effect of digoxin on the PK of JNJ-70033093.
AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours postdose. AUC (0-24) geometric mean ratio of Treatment C (JNJ-70033093 + digoxin) relative to Treatment B (digoxin) will be reported to assess the effect of JNJ-70033093 on the PK of digoxin.
| Arm | Type | Description |
|---|---|---|
| Group A: JNJ-70033093 25 mg + Placebo BID | EXPERIMENTAL | Participants will receive JNJ-70033093 25 milligram (mg) (1\*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days. |
| Group B: JNJ-70033093 50 mg BID | EXPERIMENTAL | Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days. |
| Group C: JNJ-70033093 100 mg + Placebo BID | EXPERIMENTAL | Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days. |
| Group D: JNJ-70033093 200 mg BID | EXPERIMENTAL | Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID orally for 10 to 14 postoperative days. |
| Group E: JNJ-70033093 25 mg Once Daily + Placebo | EXPERIMENTAL | Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. |
| Group F: JNJ-70033093 200 mg Once Daily + Placebo | EXPERIMENTAL | Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. |
| Group G: JNJ-70033093 50 mg once daily + Placebo | EXPERIMENTAL | Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. |
| Group I: Enoxaparin 40 mg Once Daily | ACTIVE_COMPARATOR | Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days. |
| Part 1: Cohort A: JNJ-70033093 | EXPERIMENTAL | Participants will receive Dose 1 of JNJ-70033093 once daily (QD) on Day 1 followed by washout period of 4 days and then Dose 1 of JNJ-70033093 QD from Days 5 to 12. |
| Part 1: Cohort B: JNJ-70033093 | EXPERIMENTAL | Participants will receive Dose 1 of JNJ-70033093 twice daily (BID) from Days 1 to 8. |
| Part 1: Cohort C: JNJ-70033093 | EXPERIMENTAL | Participants will receive Dose 2 of JNJ-70033093 BID from Days 1 to 8. |
| Part 2: Cohort D: JNJ-70033093 | EXPERIMENTAL | Participants will receive Dose 3 of JNJ-70033093 QD on Day 1 followed by washout period of 4 days and then Dose 3 of JNJ-70033093 BID from Days 5 to 12 in Cohort D. Dose escalation to Part 2: Cohort D will occur only after the safety and tolerability data of the Part 1 are assessed. |
| Part 1: Treatment Sequence ABC | EXPERIMENTAL | Participants will receive a single dose of JNJ-70033093 spray-dried dispersion (SDD) tablet under fasted conditions (Treatment A) in Treatment Period 1, followed by JNJ-70033093 SDD tablet in fed conditions (Treatment B) in Treatment Period 2, and then JNJ-70033093 SDD granule capsule under fasted conditions (Treatment C) in Treatment Period 3 on Day 1 of each Period during Part 1. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 1: Treatment Sequence BCA | EXPERIMENTAL | Participants will receive Treatment B in Treatment Period 1, followed by Treatment C in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1 of each Period during Part 1. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 1: Treatment Sequence CAB | EXPERIMENTAL | Participants will receive Treatment C in Treatment Period 1, followed by Treatment A in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1 of each Period during Part 1. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 1: Treatment Sequence ACB | EXPERIMENTAL | Participants will receive Treatment A in Treatment Period 1, followed by Treatment C in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1 of each Period during Part 1. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 1: Treatment Sequence BAC | EXPERIMENTAL | Participants will receive Treatment B in Treatment Period 1, followed by Treatment A in Treatment Period 2, and then Treatment C in Treatment Period 3 on Day 1 of each Period during Part 1. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 1: Treatment Sequence CBA | EXPERIMENTAL | Participants will receive Treatment C in Treatment Period 1, followed by Treatment B in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1 of each Period during Part 1. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 2: Treatment Sequence DE | EXPERIMENTAL | Participants will receive Treatment D (single dose of JNJ-70033093 SDD tablet in fed conditions) in Treatment Period 1, and then Treatment E (single dose of JNJ-70033093 SDD granule capsule under fasted conditions) in Treatment Period 2 on Day 1 of each Period during Part 2. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 2: Treatment Sequence ED | EXPERIMENTAL | Participants will receive Treatment E in Treatment Period 1, and then Treatment D in Treatment Period 2 on Day 1 of each Period during Part 2. There will be a wash-out period of at least 5 days and up to 2 weeks between Day 1 of each treatment period. |
| Part 1: Treatment A | EXPERIMENTAL | Participants will receive JNJ-70033093 dose twice daily (BID) for 8 days followed by a placebo dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9. |
| Part 1: Treatment B | EXPERIMENTAL | Participants will receive JNJ-70033093 dose BID for 8 days followed by a placebo dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9. |
| Part 1: Treatment C | EXPERIMENTAL | Participants will receive JNJ-70033093 dose BID for 8 days followed by a JNJ-70033093 dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9. |
| Part 1: Treatment D | EXPERIMENTAL | Participants will receive JNJ-70033093 dose BID for 8 days followed by a JNJ-70033093 dose on Day 9 or placebo BID for 8 days followed by a placebo dose on Day 9. |
| Part 2: Treatment Sequence EFG | EXPERIMENTAL | Participants will receive Treatment E (JNJ-7003309 single dose in the morning in fasted condition) in treatment Period 1; followed by Treatment F (JNJ-7003309 single dose administered in the evening in fasted condition) in treatment Period 2; followed by Treatment G (JNJ-7003309 single dose administered in the evening in fasted condition) in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period. |
| Part 2: Treatment Sequence FGE | EXPERIMENTAL | Participants will receive Treatment F in treatment Period 1; followed by Treatment G in treatment Period 2; followed by Treatment E in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period. |
| Part 2: Treatment Sequence GEF | EXPERIMENTAL | Participants will receive Treatment G in treatment Period 1; followed by Treatment E in treatment Period 2; followed by Treatment F in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period |
| Part 2: Treatment Sequence EGF | EXPERIMENTAL | Participants will receive Treatment E in treatment Period 1; followed by Treatment G in treatment Period 2; followed by Treatment F in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period |
| Part 2: Treatment Sequence GFE | EXPERIMENTAL | Participants will receive Treatment G in treatment Period 1; followed by Treatment F in treatment Period 2; followed by Treatment E in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period |
| Part 2: Treatment Sequence FEG | EXPERIMENTAL | Participants will receive Treatment F in treatment Period 1; followed by Treatment E in treatment Period 2; followed by Treatment G in treatment Period 3, on Day 1 of each treatment period. A washout period of at least 4 days will be maintained between each treatment period |
| JNJ-70033093 + Digoxin | EXPERIMENTAL | Participants will receive JNJ-70033093 as oral capsules (Treatment A) in Period 1, followed by digoxin tablets as loading dose and maintenance doses (Treatment B) in Period 2, and then digoxin tablets along with JNJ-70033093 (Treatment C) in Period 3. There will be a washout period of minimum 5 days (and maximum 7 days) between the last dosing day of Period 1 and the first dosing day of Period 2. There is no washout between Periods 2 and 3 (that is, the last day of Treatment B is to be followed by the first day of Treatment C). |
| Name | Type | Description |
|---|---|---|
| JNJ-70033093 25 mg | DRUG | Participants will receive JNJ-70033093 25 mg (1\*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days. |
| JNJ-70033093 50 mg | DRUG | Participants will receive JNJ-70033093 50 mg (2\*25 mg capsules) BID orally for 10 to 14 postoperative days. |
| JNJ-70033093 100 mg | DRUG | Participants will receive JNJ-70033093 100 mg (1\*100 mg capsule) BID, orally for 10 to 14 postoperative days. |
| JNJ-70033093 200 mg | DRUG | Participants will receive JNJ-70033093 200 mg (2\*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days. |
| Placebo | DRUG | Participants will receive placebo matching to JNJ-70033093, orally. |
| Enoxaparin 40 mg | DRUG | Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days. |
| JNJ-70033093 | DRUG | JNJ-70033093 capsule will be administered orally as per assigned treatment regimen. |
| Digoxin | DRUG | Participants will receive digoxin orally. |
Inclusion Criteria: * Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery * Medically stable and appro...
JNJ-70033093 is an investigational small molecule being studied for the prevention of blood clots in patients undergoing elective total knee replacement surgery. It has been evaluated in a Phase 2 clinical trial comparing it to subcutaneous enoxaparin in this setting. The drug is also being studied in healthy volunteers to assess its safety and pharmacokinetics.
JNJ-70033093 is being developed by Johnson & Johnson, a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol JNJ. The drug is also known as BMS-986177, reflecting its earlier development by Bristol-Myers Squibb before being acquired by Johnson & Johnson.
JNJ-70033093 is in Phase 2 clinical development. A Phase 2 trial in patients undergoing elective total knee replacement surgery has been completed, along with three Phase 1 studies in healthy volunteers. The drug is not approved and remains investigational.
JNJ-70033093 has been studied in four completed clinical trials. The Phase 2 trial NCT03891524 enrolled 1,242 patients undergoing elective total knee replacement surgery. Phase 1 trials include NCT04206488, NCT04223349, and NCT04448964, which evaluated the drug in healthy volunteers.
Yes, JNJ-70033093 is also known as BMS-986177. The drug was originally developed by Bristol-Myers Squibb and is now being developed by Johnson & Johnson. Both names refer to the same investigational small molecule.