Symptoms and General Pathology

All Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Rare Diseases

Syndrome

Cushing Syndrome

Hypersensitivity

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Endocrine System Diseases

Cushing's Syndrome

Hyperadrenalism

Anticoagulants

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Amino Acids

Dabigatran

polysaccharide-K

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Enzyme Inhibitors

Serine

Following an overnight fast, participants will receive 75 mg dabigatran etexilate on Day 1, 400 mg dose of relacorilant QD on Days 3 to 13, and 75 mg dabigatran etexilate on Day 12. On Day 12, dabigatran etexilate will be dosed at approximately the same time as the relacorilant dose.

Dabigatran will be administered orally as a 75 mg capsule on Day 1 and Day 12.

Dabigatran Etexilate

Relacorilant will be administered orally as 4 X 100 mg capsules (400 mg) on Days 3 through 13.

Relacorilant

Joseph Custodio, PhD

The primary objective is to determine the effect of relacorilant on the pharmacokinetics (PK) of the sensitive P-glycoprotein (P-gp) substrate dabigatran etexilate.

The investigational medicinal product (IMP), relacorilant, and the non-investigational medicinal product (NIMP), dabigatran etexilate, will be used to evaluate the effect of relacorilant on the PK of the sensitive P-gp substrate, dabigatran etexilate in healthy participants. Participants will receive a single dose of dabigatran etexilate before and after administration of daily (QD) doses of relacorilant for 11 days. As all participants will receive the same treatments, the study will be open-label and no randomization is required.

Effect of Relacorilant on the Pharmacokinetics of the Sensitive P-glycoprotein Substrate Dabigatran Etexilate in Healthy Participants

An Open-Label, Drug-Drug Interaction Study Designed to Evaluate the Effect of Relacorilant on the Pharmacokinetics of the Sensitive P-glycoprotein Substrate Dabigatran Etexilate in Healthy Subjects

Corcept Therapeutics

Neoplasms

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Lipid Regulating Agents

Bone Density Conservation Agents

Rosuvastatin Calcium

Calcium

Calcium, Dietary

Anticholesteremic Agents

Hypolipidemic Agents

Antimetabolites

Hydroxymethylglutaryl-CoA Reductase Inhibitors

On Day 1, a single oral dose of dabigatran etexilate 150 mg will be given under fasted conditions and serial PK samples will be collected as indicated on the schedule of events. On Day 5, subjects will receive a single oral dose of fruquintinib 5 mg at approximately 1 hour prior to administration of a single oral dose of dabigatran etexilate 150 mg under fasted conditions and serial PK samples will be collected

On Day 1, a single oral dose of rosuvastatin 10 mg will be given under fasted conditions and serial PK samples will be collected as indicated on the schedule of events. On Day 5, subjects will receive a single oral dose of rosuvastatin 10 mg with fruquintinib 5 mg under fasted conditions and serial PK samples will be collected

Fruquintinib will be administered as a single oral 5mg dose on the morning of day 5

Fruquintinib

Dabigatran Etexilate will be administered as a single oral dose 150mg on the morning of day 1 and morning of day 5

Rosuvastatin will be administered as a single oral dose 10mg on the morning of day 1 and the morning of day 5

Rosuvastatin

Fruquintinib DDI Study with P-gp and BCRP Substrates

A phase 1, open-label, 2-part, 2-period fixed-sequence study to evaluate the effect of Fruquintinib on the pharmacokinetics of Dabigatran Etexilate (A P-GP substrate) and Rosuvastatin (A BCRP substrate) in healthy subjects

Fruquintinib DDI Study With P-gp and BCRP Substrates

A Phase 1, Open-label, 2-part, 2-period Fixed-sequence Study to Evaluate the Effect of Fruquintinib on the Pharmacokinetics of Dabigatran Etexilate (A P-GP Substrate) and Rosuvastatin (A BCRP Substrate) in Healthy Subjects

area under the plasma concentration-time curve from time 0 to time of the last measurable concentration

area under the plasma concentration-time curve from time 0 to infinity (if data permit)

Any untoward medical occurrence associated with the use of study drug

Hutchmed

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Tepotinib

Participants received single oral dose of Dabigatran etexilate on Day 1 of Treatment period 1 and co-administration of Dabigatran with Tepotinib on Day 8 of Treatment period 2.

Participants received single oral dose of Tepotinib for 8 days in Treatment period 2.

Medical Responsible

This study investigated the effect of Tepotinib on the pharmacokinetics (PK) of the p-glycoprotein (P-gp) probe substrate Dabigatran etexilate.

Effect of Tepotinib on the PK of the P-gp Substrate Dabigatran Etexilate

Phase I, Open-label, Single Sequence, Two-Period Study to Evaluate the Effect of Tepotinib on P-gp by Investigating the PK of the P-gp Probe Substrate Dabigatran Etexilate in Healthy Subjects

AUC0-t was calculated according to the mixed log linear trapezoidal rule.

AUC0-inf was calculated as AUC0-t plus (+) AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/Lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log-linear regression line for Lambda z determination at which the measured plasma concentration is at or above Lower limit of quantification (LLOQ).

Cmax was obtained directly from the concentration versus time curve.

Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.

Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/f after oral dose was influenced by the fraction absorbed.

The AUC from time tlast extrapolated to infinity given as percentage of AUC0-inf. AUCextra% = (AUCextra /AUC0-inf)\*100.

Adverse event (AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event (SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs.

Number of participants with clinically significant change in laboratory values were reported. Clinical significance was decided by the investigator. Laboratory investigation included hematology, biochemistry, virology, drugs of abuse, hormones, urinalysis, and coagulation.

Number of participants with clinically significant change in 12-lead ECG were reported. Clinical significance was decided by the investigator. The 12-lead ECGs were recorded after the participant have rested for at least 5 minutes in supine position.

Number of participants with clinically significant change in vital signs were reported. Clinical significance was decided by the investigator. Vital signs included body temperature, blood pressure, and pulse rate.

Merck KGaA, Darmstadt, Germany

Participants received a single oral dose of 75 milligrams (mg) dabigatran etexilate capsule on Day 1 under fed state in treatment period 1.

All participants who received 75 mg Dabigatran Etexilate in treatment period 1, received oral dose of 500 mg tepotinib film-coated tablets from Day 1 to 8 under fed state along with 75 mg dabigatran etexilate on Day 8 of treatment period 2.

Tepotinib + Dabigatran

All participants who received a single oral dose of 75 mg dabigatran etexilate capsule in treatment period 1 and 500 mg tepotinib (500 mg) film coated tablet from Day 1 to 8 along with 75 mg dabigatran etexilate Capsule in treatment period 2 under fed state.

All Participants

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Communication Center

Pharmacokinetic (PK) analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Total Dabigatran

PK analysis set: all participants who completed at least 1 period without any relevant protocol violations with respect to factors affecting comparability of PK results with adequate study drug compliance and evaluable dabigatran PK data. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Total Dabigatran

Maximum Observed Plasma Concentration (Cmax) of Total Dabigatran

Time to Reach Maximum Plasma Concentration (Tmax) of Total Dabigatran

Elimination Half Life (t1/2) of Total Dabigatran

Apparent Clearance (CL/f) of Total Dabigatran

Apparent Volume of Distribution During Terminal Phase (Vz/f) of Total Dabigatran

Percentage of Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUC0-inf) Obtained by Extrapolation (AUCextra%) of Total Dabigatran

Treatment-emergent Adverse Events (TEAEs)

Serious TEAEs

The safety analysis set included all participants who received at least 1 dose of the planned investigational medicinal product (IMP).

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

The safety analysis set included all participants who received at least 1 dose of the planned IMP.

Number of Participants With Clinically Significant Changes in Laboratory Values

Number of Participants With Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Findings

Number of Participants With Clinically Significant Changes in Vital Signs

Treatment Period 1

Treatment Period 2

Skin and Connective Tissue Diseases

Breast Neoplasms

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Midazolam

Omeprazole

Celecoxib

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Participants will receive single oral doses of midazolam and omeprazole together (Day 1 of Treatment Periods 1 and 3) and repeated doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3)

Participants will receive single oral doses of dabigatran etexilate (Day 1 of Treatment Periods 1 and 2) and single oral dose of AZD9833 (Day 1 of Treatment Period 2)

Participants will receive single oral doses of celecoxib (Day 1 of Treatment Periods 1 and 3) and repeated oral doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3)

AZD9833 tablets will be administered orally once daily on Days 1 - Day 5 (Treatment Period 2) and Day 1 (Treatment Period 3) for participants recruited to Arms A and C and Day 1 for those in Arm B

AZD9833

Midazolam will be administered orally as a syrup once on Day 1 of Treatment Periods 1 and 3; administered together with Omeprazole

An Omeprazole capsule will be administered once on Day 1 of Treatment Periods 1 and 3; administered together with Midazolam

A Dabigatran Etexilate capsule will be administered once on Day 1 of Treatment Periods 1 and 2

A Celecoxib capsule will be administered once on Day 1 of Treatment Periods 1 and 3

This study will be a fixed sequence drug-drug interaction study in healthy postmenopausal females, conducted at multiple study sites

Participants will be randomized to one of 3 treatment arms on Day 1 prior to Investigational Medicinal Product (IMP) administration:

* Arm A: single oral doses of midazolam and omeprazole administered together + repeated doses of AZD9833 .
* Arm B: single oral doses of dabigatran etexilate + single oral dose of AZD9833 .
* Arm C: single oral doses of celecoxib + repeated oral doses of AZD9833.

Each participant will be involved in the study for up to 7 to 8 weeks

Study to Assess the Effect of Co-Administration of AZD9833 on the Pharmacokinetics of Midazolam, of Omeprazole, of Celecoxib and of Dabigatran Etexilate in Healthy Postmenopausal Female Volunteers

A Phase 1, Multi-center, Open-label, 3-arm, Fixed Sequence Study to Assess the Effect of Co-administration of AZD9833 on the Pharmacokinetics of Midazolam (CYP3A4/5 Substrate), of Omeprazole (CYP2C19 Substrate), of Celecoxib (CYP2C9 Substrate) and of Dabigatran Etexilate (P-gp Transporter Substrate) in Healthy Postmenopausal Female Volunteers

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic (PK) variables of: - single-dose midazolam and omeprazole, administered together

* single-dose dabigatran etexilate
* single-dose celecoxib

The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of:

* single-dose midazolam and omeprazole, administered together
* single-dose dabigatran etexilate
* single-dose celecoxib

The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of:

* single-dose midazolam and omeprazole administered together
* single-dose dabigatran etexilate
* single-dose celecoxib

The safety and tolerability of AZD9833, alone and in combination with midazolam, omeprazole, dabigatran etexilate, and celecoxib will be evaluated in healthy postmenopausal female participants.

AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate will be further characterized.

AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate, and will be further characterized.

AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate will be further characterized

AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

AstraZeneca

Heart and Blood Diseases

Thrombosis

Pulmonary Embolism

Embolism

Thromboembolism

Venous Thromboembolism

Venous Thrombosis

Embolism and Thrombosis

Vascular Diseases

Lung Diseases

Respiratory Tract Diseases

Fibrinolytic Agents

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Heparin

Calcium heparin

Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed dabigatran 150mg twice daily from Day 6 onward till 6 months after underlying disease remission.

Dabigatran etexilate

Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed

Gloria Hwang, MBBS

Crosby Lu, MMedSc

This trial aims at determining if dabigatran is effective in the treatment of malignancy associated VTE. Tolerance and safety of dabigatran will also be assessed.

This is a single armed trial of dabigatran in patients with malignancy associated VTE.

The target recruitment is 99 consecutive patients with active malignancy and newly diagnosed VTE (deep vein thrombosis and/or pulmonary embolism) in Queen Mary Hospital.

Tinzaparin 175 iu/kg daily will be started after the diagnosis of VTE is confirmed (duplex Doppler ultrasonography for deep vein thrombosis, and computed tomography for pulmonary embolism), and a written consent is obtained. Patients will be switched to dabigatran 150mg twice daily from day 6 onwards. The first dose of dabigatran will be given within 2 hours before the time that the next dose of tinzaparin would have been due. Anticoagulation will be continued as long as malignancy is active. If patients achieve a complete remission of their underlying malignancies, dabigatran will be continued for 6 months further.

Patients with malignancies are at increased risks of venous thromboembolism (VTE). The annual incidence of VTE in cancer patients is 0.5%, which is 5-fold more than the general population . Low molecular weight heparin (LMWH) has been the standard treatment for malignancy-associated VTE. This recommendation follows the results of the Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent VenousThromboembolism in Patients with Cancer (CLOT) trial, which showed superiority of Low molecular weight heparin (LMWH) over warfarin in cancer patients with VTE .

Low molecular weight heparin (LMWH) has a number of inherent advantages over warfarin. It does not interact with chemotherapeutic agents, and dose titration is not necessary. Furthermore, the risks of both bleeding and breakthrough VTE are also lower with LMWH. However, the requirement of daily subcutaneous injection makes LWMH inconvenient to use. Most patients have difficulties continuing daily injection, partly owing to compliance issues, but also because an emaciated state in some patients makes subcutaneous injection painful. As the life expectancy of solid cancer patients is improved with novel treatment options, the choice of anticoagulation has become a major issue in the management of VTE in this patient population.

The main reason underlying the inferior performance of warfarin in oncology patients is difficult dose titration. Drug interaction and hepatic dysfunction are common in patients on chemotherapy. Frequent interruptions of warfarin for invasive procedures and chemotherapy-induced-thrombocytopenia also lead to fluctuations in anticoagulation level. As a result, highs risk of recurrence of VTE and bleeding were observed in cancer patients taking warfarin. Direct-acting oral anticoagulants (DOACs), on the other hand, may be an attractive alternative treatment to LMWH. They are administered at a fixed dose with predictable pharmacokinetics, so that therapeutic monitoring is not required. There is minimal food and drug interaction. They have been shown to be effective in the treatment of VTE in several pivotal randomized controlled trials in comparison with warfarin . However, their role in malignancy associated VTE is yet to be determined, because cancer patients were either excluded or very much underrepresented in these VTE treatment trials. Moreover, the non-inferiority of DOACs in VTE treatment was only demonstrated against warfarin, which is already shown to be suboptimal in oncology patients. A trial directly comparing DOACs with LMWH in malignancy associated VTE is therefore needed.

Dabigatran etexilate is an oral thrombin inhibitor. It was shown in the RECOVER study to be effective in treatment of VTE and it has a lower bleeding risk than warfarin. It is not metabolized by cytochrome P450 system and therefore, in contrast to other DOACs, concomitant administration of CYP3A4 inducers or inhibitors is not a concern.

We propose this prospective single armed trial to evaluate the efficacy and safety of dabigatran in the treatment of malignancy associated VTE. We will compare the result with our historical control who were treated with LMWH.

A Study of Dabigatran Etexilate as Primary Treatment of Malignancy Associated Venous Thromboembolism

A Prospective Study of Dabigatran Etexilate as Primary Treatment of Malignancy Associated Venous Thromboembolism

first episode of objectively documented symptomatic recurrent VTE (deep vein thrombosis, pulmonary embolism)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effect of Relacorilant on the Pharmacokinetics of the Sensitive P-glycoprotein Substrate Dabigatran Etexilate in Healthy Participants	NCT05347979	Cushing Syndrom... Neoplasms	Dabigatran Etex... Relacorilant	18 Years - 55 Years	Corcept Therapeutics
Fruquintinib DDI Study With P-gp and BCRP Substrates	NCT05368805	Metastatic Colo...	Fruquintinib Dabigatran Etex... Rosuvastatin	18 Years - 55 Years	Hutchmed
Effect of Tepotinib on the PK of the P-gp Substrate Dabigatran Etexilate	NCT03492437	Healthy	Dabigatran Etex... Tepotinib	18 Years - 44 Years	Merck KGaA, Darmstadt, Germany
Study to Assess the Effect of Co-Administration of AZD9833 on the Pharmacokinetics of Midazolam, of Omeprazole, of Celecoxib and of Dabigatran Etexilate in Healthy Postmenopausal Female Volunteers	NCT05438303	Healthy Volunte...	AZD9833 Midazolam Omeprazole Dabigatran Etex... Celecoxib	50 Years - 70 Years	AstraZeneca
Study to Assess the Effect of Co-Administration of AZD9833 on the Pharmacokinetics of Midazolam, of Omeprazole, of Celecoxib and of Dabigatran Etexilate in Healthy Postmenopausal Female Volunteers	NCT05438303	Healthy Volunte...	AZD9833 Midazolam Omeprazole Dabigatran Etex... Celecoxib	50 Years - 70 Years	AstraZeneca
Effect of Relacorilant on the Pharmacokinetics of the Sensitive P-glycoprotein Substrate Dabigatran Etexilate in Healthy Participants	NCT05347979	Cushing Syndrom... Neoplasms	Dabigatran Etex... Relacorilant	18 Years - 55 Years	Corcept Therapeutics
A Study of Dabigatran Etexilate as Primary Treatment of Malignancy Associated Venous Thromboembolism	NCT03240120	Venous Thromboe... Deep Vein Throm... Pulmonary Embol...	Dabigatran etex... Tinzaparin	18 Years -	The University of Hong Kong
Dabigatran Etexilate for Secondary Stroke Prevention in Patients With Embolic Stroke of Undetermined Source (RE-SPECT ESUS)	NCT02239120	Stroke Secondary Preve...	optional ASA as... placebo to ASA placebo to opti... placebo to dabi... ASA 100 mg dabigatran etex...	18 Years - 150 Years	Boehringer Ingelheim

Spots Global Cancer Trial Database for dabigatran etexilate