"Corticoid-16" in Long Term When Administered Systemically in Patients in Routine Medical Practice

Pharmacological Action Clinical Trial

Official title:

Evaluation of Pharmacokinetic Parameters of "Diprospan"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03119454
• Other study ID #: RU-FANO-10-16
• Status: Completed
• Phase: N/A
• First received: December 9, 2016
• Last updated: April 13, 2017
• Start date: October 2016
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: Federal State Budgetary Scientific Institution, Scientific Research Institute of Rheumatology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Evaluation of pharmacokinetic parameters of diprospan in long term when administered systemically in patients in routine medical practice.

Applied research project.

Design: open-comparative prospective cohort study.

Two groups of subjects:

• patients who are receiving diprospan in standard therapy of their existing disease, or multiple times, but following the introduction of diprospan is planned no earlier than 28 days after the first,

• control group of subjects for the study of pharmacokinetic parameters diprospan and its metabolites.

Objectives of the study: to evaluate the pharmacokinetic parameters of Diprospan in the long term when administered systemically in patients in routine practice.

Description:

Design: Open-comparative prospective cohort study.

The study population: two groups of subjects

• first group: patients who are receiving diprospan in standard therapy of their existing disease, or multiple times, but following the introduction of diprospan is planned no earlier than 28 days after the first administration.

• second group: the control group of subjects for the study of pharmacokinetic parameters diprospan and its metabolites.

Intramuscular injection diprospan (suspension for injection) at a dose of 1 ml (7 mg) once.

Main objective of the study: to evaluate pharmacokinetic parameters of Diprospan in the long term when administered systemically in patients in routine practice.

Objectives of the study:

• to develop laboratory analytical method of quantifying the investigated substance (betamethasone) in human urine sensitive, selective and precise method using high performance liquid chromatography with tandem mass selective detection,

• analysis of quantitative content, evaluation of pharmacokinetic parameters of diprospan in the bioassay in patients with systemic intramuscular application in routine clinical practice in the Russian Federation,

• analysis of clinical patient data and pharmacokinetic parameters of study drug in the urine of patients,

• determination of minimum number of arbitration bioassay to store,

• preparation of recommendations for systemic use of glucocorticoids in athletes, in accordance with the requirements of the all-Russian anti-doping rules and the requirements of the anti-doping rules, approved by the international anti-doping authorities.

First group (patients receiving diprospan).

Stage 1: selection of study participants from a number of patients who are administered with Diprospan" at a dose of 1 ml (7 mg) intramuscularly as standard therapy of existing disease, or multiple times, but following introduction of "Diprospan" drug is planned no earlier than 28 days after the first.

Step 2: draw the original samples for pharmacokinetic studies, a single injection of the study medication as part of routine care.

Stage 3: Sampling in dynamics for pharmacokinetic studies; assessment of clinical and laboratory parameters after a single administration of the study drug.

Stage 4: evaluation of clinical examination data and pharmacokinetic study.

Second group (control).

Stage 1: selection of study participants from a number of patients or healthy volunteers who had not received systemic or local corticosteroids in the last 12 weeks before the screening visit.

Stage 2: drawing of samples for pharmacokinetic studies.

Primary endpoints:

• betamethasone concentration in urine.

Secondary endpoints:

• evaluation of articular status,

• overall assessment of the health status of the patient,

• overall assessment of disease activity, physician assessment of disease activity criteria for SDAI, CDAI, DAS-28.

Number of patients.

First group (the study of the pharmacokinetics of the drug "Diprrospan"): at least 20 patients (10 men and 10 women).

The second group (control): at least 20 patients (10 men and 10 women).

Safety monitoring In accordance with the order of the Health Ministry of Russia №757n "Approval of the Procedure for monitoring the safety of medicinal products for medical use, registration of adverse events, serious adverse reactions, unexpected adverse reactions in the use of drugs for medical use."

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Signed a voluntary informed consent form,

• Patients of both sexes aged 18 to 35 years old Caucasian,

• Verified diagnosis of rheumatoid arthritis according to criteria ACR \ EULAR 2010 or ankylosing spondylitis (axial spondyloarthritis) ASAS criteria for 2009 based on the data a detailed medical history, a standard clinical, laboratory and instrumental methods of examination,

• The presence of signs of active inflammation according to standard valuation techniques (for rheumatoid arthritis or DAS28 =3.2 CDAI=10; for ankylosing spondylitis or BASDAI=2.0 ASDAS=1.3),

• If the patient gets authorized for use in the study antirheumatic drugs (except glucocorticoids other) for treatment of the underlying disease, they should be applied in stable doses for at least six weeks before the screening visit.

• BMI should be in the range of 18.0 to 30.0 kg / m 2 ,

• Consent to use adequate methods of contraception to patients during the study period.

Exclusion Criteria:

• Allergic history,

• Drug intolerance, hypersensitivity to any of the components "Diprospan" drug,

• Severe chronic cardiovascular, bronchopulmonary, endocrine and nervous systems (including mental) and diseases of the gastrointestinal tract (GIT), liver, kidney, blood, surgical procedures on the gastrointestinal tract (except appendectomy)

• Acute infectious, non-infectious and allergic diseases in less than 4 weeks prior to visit 1,

• A positive blood test for HIV, syphilis, hepatitis B and C,

• Systolic blood pressure measured at rest after 5 minutes of exposure in the "sitting" position, below 100 mm Hg. or above 140 mm Hg and / or diastolic blood pressure below 60 mm Hg or above 90 mm Hg,

• Heart rate below 40 beats / min,

• Hemoglobin <90 g / l (9 g / dl), or hematocrit less than 30%,

• White blood cells <3.0 x 10 9 / L,

• Absolute neutrophil count (ANC) <1.0 x 10 / L,

• Serum creatinine more than 0.132 mmol / L,

• Increased ALT and / or AST 1.5 upper limit of normal,

• Clinically significant (in the opinion of the investigator) ECG changes,

• The use of systemic or local corticosteroids for the treatment of the underlying disease for the last 12 weeks before the screening visit,

• Taking any medications, in addition to permissible under study

• Plasmapheresis in less than 14 days prior to study entry,

• Participation in a clinical trial of an unregistered in the Russian Federation of a drug or device for less than 3 months prior to the study,

• The inability or unwillingness of the patient to comply with the conditions of the study program,

• Any reason for that, according to the researcher, will prevent the participation of the patient in the study,

• Pregnant or lactating women (all women should have a negative pregnancy test on the day of screening).

Related Conditions & MeSH terms

• Pharmacological Action

Intervention

Drug:
• Diprospan
Intramuscular

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Federal State Budgetary Scientific Institution, Scientific Research Institute of Rheumatology	Institute of Biomedical Chemistry, Russia, The League of Clinical Research, Russia

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall assessment of the health status of the patient by physician	Vital signs, physical examination, new diagnoses	Day 28
Other	Overall assessment of the health status of the patient by patient	Visual analogue scale, mm	Day 28
Primary	Betamethasone concentration in urine	Quantitative determination of study drug (betamethasone) in human urine should be conducted sensitive, selective and precise method using high performance liquid chromatography with tandem mass selective detection (HPLC-MS / MS) with a detection mode permits fragment ions not more R <70K. laboratory analytical method should be developed for the measurement of betamethasone with the definition of the limit of not less than 7.5 ng / mL.	Day 28
Secondary	Articular status (swelling)	Number of swollen joints	Day 28
Secondary	Articular status (pain)	Number of painful joints	Day 28
Secondary	Physician's assessment of disease activity	Visual analogue scale, mm	Day 28
Secondary	Simple disease activity index SDAI	Scale: remission; low activity; moderate activity; high activity	Day 28
Secondary	Clinical disease activity index CDAI	Scale: remission; low activity; moderate activity; high activity	Day 28
Secondary	Disease activity score DAS28	Scale: remission; low activity; moderate activity; high activity	Day 28