Captopril 5 mg/mL oral solution is a new oral pharmaceutical formulation intended for the treatment of congestive heart failure in male and female paediatric patients from birth to 18 years.
Conditions
Interventions
Product Name: Captopril oral solution 5 mg/mL
Pharmaceutical Form: Oral solution
INN or Proposed INN: Captopril
CAS Number: 62571-86-2
O
Sponsors
Proveca Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed informed consent including data protection declaration prior to study participation. 2.Healthy male and female volunteers. Women of childbearing potential (pre-menopausal, not surgically sterile for at least 3 months prior to the time of screening) must use a highly effective contraceptive method throughout the study such as: implants, injectables, hormonal contraceptives and condom or double barrier contraception (i.e., condom + diaphragm/spermicidal gel or foam), sexual abstinence or vasectomised partner and must have a confirmed negative pregnancy test at Screening Visit. Men must use safe contraceptive measures (i.e., condom/spermicidal gel or foam, sexual abstinence or be vasectomised) during the study. 3.Subjects aged =18 and =55 years at screening. 4.Caucasian (at least one parent of Caucasian origin). 5.Body Mass Index =18.5 and =30.0 kg/m2. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.History or presence of any clinically significant gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel disease, major surgery of the gastrointestinal tract, gastroduodenal ulcer, or previous or active gastrointestinal bleeding), unresolved gastrointestinal symptoms (e.g., diarrhoea, vomiting), liver or kidney disease or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug. 2.Any clinically significant abnormality identified on physical examination, laboratory tests, ECG or vital signs at the time of screening that in the judgment of the Investigator would preclude safe completion of the study or constrain pharmacokinetic assessment. 3.History or presence of asthma (including aspirin-induced asthma) or nasal polyps. 4.History of angioneurotic oedema associated with previous ACE (angiotensin-1 converting enzyme) inhibitor therapy, or hereditary/idiopathic angioneurotic oedema. 5.Any planned procedures, diagnostic tests or hospital admissions during the study duration. 6.Positive results of HBsAg, anti-HCV, anti-HIV tests. 7.Intake or administration of any systemic or topical medication (including multivitamin or mineral preparations), OTC (over the counter) or herbal dietary supplements (e.g., St. John's Worth, kava kava), within 4 weeks prior to the start of the study, when the terminal elimination half-life of these products does not allow for their complete elimination from the body before the beginning of the study. An exception is hormonal contraceptives for women with childbearing potential. 8.History of severe allergy or allergic reactions to the study drug or related drugs (any other ACE inhibitor) and products (including excipients of the formulations, for example lactose). 9.History of significant alcohol abuse within six months of the Screening Visit or any indication of the regular use of more than two units of alcohol per day (1 unit = 150 mL of wine or 360 mL of beer or 45 mL of 40% alcohol). 10.Presence of metabolites of illicit drugs in urine during screening procedures. 11.Breastfeeding. 12.Smoking. 13.Blood donation within 3 months prior to administration of the study medication. 14.Use of an investigational drug or participation in an investigational study within 90 days prior to administration of the study medication. 15.Volunteers in custody by juridical or official order. 16.Volunteers who have difficulties in understanding the language in which the volunteer information is given. 17.Volunteers who do not agree to the transmission of their anonymous data within the liability of documentation and notification. 18.Staff of the study centre, staff of the Sponsor or CRO, the Investigator himself or close relatives of the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To assess the comparative bioavailability of Captopril oral solution 5 mg/mL relative to Captopril Qualigen 25 mg tablets, when administered as a single dose of 25 mg. ; Primary end point(s): Primary PK parameters •AUC0-t: Area under the plasma concentration-time curve from time 0h to the last measurable concentration. •Cmax: Observed maximum plasma concentration (peak exposure). ; Secondary Objective: •To investigate the effect of food on the pharmacokinetics of Captopril oral solution 5 mg/mL in healthy volunteers after a single dose of 25 mg. •To evaluate the taste acceptability including sweet or bitter tasting, granular or smooth in texture and pleasant or unpleasant flavour of Captopril oral solution 5 mg/mL. •To assess the safety and tolerability of Captopril oral solution 5 mg/mL and Captopril Qualigen 25 mg tablets ;Timepoint(s) of evaluation of this end point: For this study, captopril will be quantified in plasma samples. Blood samples will be collected at 17 time-points (t) from each subject at each study period at the following sampling timepoints: predose and at t15min, t30min, t45min, t1h, t1h15min, t1h30min, t1h45min, t2h, t2h30min, t3h, t4h, t5h, t6h, t8h, t10h and t12h after dosing. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary PK parameters •AUC0-8: Area under the plasma concentration-time curve (from time 0 to infinity), extrapolated to terminal elimination. •AUCt-8: Residual area (extrapolated portion of plasma captopril-time curve). •tmax: Time to reach Cmax (time to peak exposure). •Kel: Drug elimination rate constant. •t½: Drug elimination half-life. Assessment of food effect The effect of food on the pharmacokinetics of Captopril oral solution 5 mg/mL will be tested based on the Primary PK parameters (AUC0-t and Cmax). Taste acceptability assessment The taste acceptability assessment will be done immediately after administration of Captopril oral solution 5 mg/mL under fasted and fed conditions (Tfasted, Tfed). A 100-mm visual analogue scale (VAS) will be used to assess the following taste testing variables: sweet or bitter tasting, granular or smooth in texture and pleasant or unpleasant flavour. Safety and tolerability Only treatment-emergent AEs will be considered in order to assess the safety and tolerability of the formulations. Observed abnormalities with respect to vital signs (systolic/diastolic blood pressure, pulse, and body temperature), 12-lead ECG and safety laboratory tests will be documented in the CRF. ; Timepoint(s) of evaluation of this end point: Secondary PK parameters. Blood samples will be collected at 17 time-points (predose and at t15min, t30min, t45min, t1h, t1h15min, t1h30min, t1h45min, t2h, t2h30min, t3h, t4h, t5h, t6h, t8h, t10h and t12h after dosing) from each subject at each study period Assessment of food effect. Blood samples will be collected at 17 time-points (predose and at t15min, t30min, t45min, t1h, t1h15min, t1h30min, t1h45min, t2h, t2h30min, t3h, t4h, t5h, t6h, t8h, t10h and t | — |
Countries
Spain
Contacts
Public ContactClinical Trials Department
Dynakin S.L.
Outcome results
None listed