A phase I clinical trial to study the safety and tolerability of multiple doses of a new compound, RBx 10017609, in healthy volunteers

A Single-Blind, Randomized, Placebo Controlled, Rising Multiple Dose, Safety, Tolerability and Pharmacokinetic Study of RBx 10017609 in Healthy Adult Male Human Volunteers

Status

Active, not recruiting

Phases

Phase 1

Study type

Interventional

Source

CTRI

Registry ID

CTRI/2009/091/000173

Enrollment

Registered

2009-06-16

Start date

Unknown

Completion date

Unknown

Last updated

2021-11-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Interventions

Intervention1: RBx 10017609: oral tablets of 50 mg bid, 125 mg bid and 200 mg bid or 400 mg bid or 800 mg od for 28 days Control Intervention1: Placebo: oral tablets of 50 mg bid, 125 mg bid and 200 m

Eligibility

Inclusion criteria

Inclusion criteria: ? Healthy males in the age range of 18 ? 45 years with Body Mass Index (BMI*) between 19 ? 28 kg/m2. ? Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study. ? Have voluntarily given written informed consent to participate in this study. ? Be of normal health as determined by medical history, have sitting systolic blood pressure of &#8805; 100 mmHg to < 140 mmHg and diastolic blood pressure of &#8805; 60 mmHg or < 90 mmHg, pulse rate &#8805;60 & &#8804; 90 bpm, clinical examination and laboratory investigations performed within 21 days prior to the commencement of the study. *BMI = Body Weight (in kg)/ Height (in m2) Additional Inclusion criteria for healthy smokers ? Current smoker and smoking history of at least 5 pack years.* ? No history of cough with sputum production, dyspnoea especially with exercise and wheezing. ? No history of respiratory or allergic disease. ? Normal baseline spirometry as predicted for age, sex and height. ? No history of upper respiratory tract infection in the preceding six weeks. ? Not taking regular medication. * 1 pack year is 20 cigarettes/day for 1 year

Exclusion criteria

Exclusion criteria: ? History of hypersensitivity to any drug or history of allergic reactions/atopy. ? Any evidence of organ dysfunction or any clinically significant deviation from the normal, in physical or clinical determinations. ? Presence of disease markers of HIV 1 or 2, Hepatitis B or C viruses or venereal infection. ? Presence of values, which are out of acceptable limits for hemoglobin, RBC count, hematocrit, activated partial thromboplastin time (aPTT), prothrombin time (PT), total white blood cells count, differential WBC count or platelet count. ? Positive for urinary screen testing of drugs of abuse (opiates or cannabinoids). ? Presence of values which are out of acceptable limits for blood urea nitrogen (BUN), serum creatinine, uric acid, sodium, potassium, calcium, phosphorus, chloride, bicarbonate, alkaline phosphatase (ALP), aspartate amino transferase (AST), alanine amino transferase (ALT), total bilirubin, gamma glutamyl transpeptidase (GGT), albumin, globulin, total protein, cholesterol, triglycerides, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), glucose, Cystatin C and C-reactive protein. ? Clinically abnormal chemical and microscopic examination of urine. ? Clinically abnormal ECG (12 lead), QTc >440 msec and abnormal Chest X-ray. ? History of or any complaints suggestive of gastrointestinal, hepatic, renal, cardiovascular, pulmonary, neurological (including generalized or partial epilepsy), endocrine, vision abnormality, rheumatological, urogenital or hematological disease. ? Presence of significant infection or known inflammatory process. ? Presence of acute gastrointestinal symptoms at the time of screening and/or admission (e.g., nausea, vomiting, diarrhoea, heart burn). ? Presence of chronic constipation (less than 3 times a week for 12 weeks) at the time of screening and/or admission. ? Inability to communicate well with investigator (i.e. language problem, poor mental development, psychiatric illness or poor cerebral function) that may impair the ability to provide, written informed consent. ? History of joint pain, stiffness and reduced mobility ? Use of tobacco in any form (including cigarette smoking) in the last 6 months (except for healthy smoker cohorts). ? History of drug dependence or habitual alcohol abuser. ? Use of any regular medication (OTC or prescription) with in 14 days or any drug metabolizing enzyme modifying medications within 30 days prior to Day 1 of this study. ? History of intake of chronic medication. ? Participation in any clinical trial within 12 weeks preceding Day 1 of this study. ? Volunteers who, through completion of this study, would have donated and/or lost more than 350 mL of blood in the past 3 months.

Design outcomes

Primary

Measure	Time frame
Safety and tolerability assessed on the basis of AEs, vital signs (BP, pulse rate, respiratory rate and body temperature), ECG and clinical laboratory results after multiple dose administration of RBx 10017609.Timepoint: Medical history and clinical examination will be performed at screening and brief clinical examination on admission, pre-dose, approximately every 12 hours after dosing till discharge and at follow-up. Adverse event monitoring at admission, pre-dose, 1, 3, 7, 12, 13 and 14 hrs post morning dose on each day (for 28 days) and thereafter at 24, 28, 32, 36, 48, 52, 56, 60, 72, 96 and 120 hours post morning dose of day 28 and at follow-up. Vital Signs will be measured and recordings will be done at screening, on admission, pre dose, 1, 3, 7, 12, 13 and 14 hrs post morning dose on each day and thereafter every 12 hr until discharge and at follow-up and whenever Clinical Investigator/Principal Investigator feels necessary. A 12-Lead ECG will be recorded at screening, pre-dose and 2 hrs, 5 hrs, 12 hrs, and 14 hours after administration of morning dose on 1st, 3rd, 7th, 14th, 21st and 28th day, at discharge and at follow-up. Continuous lead II ECG will be done for first three hours post dose on day 1-3 and upon the judgement of investigator. Haematology, biochemistry, urinalysis will be performed at screening, admission, prior to morning dose on Day 7, 14, 21 and 28, discharge, follow up and at appropriate intervals throughout the study. Ultrasound upper abdomen will be carried out prior to admission and on the day of discharge. Vital signs, 12 lead ECG, safety assessment and adverse event monitoring will be carried out approximately ± 1.5 hours of the scheduled time.	—

Measure

Time frame

Safety and tolerability assessed on the basis of AEs, vital signs (BP, pulse rate, respiratory rate and body temperature), ECG and clinical laboratory results after multiple dose administration of RBx 10017609.Timepoint: Medical history and clinical examination will be performed at screening and brief clinical examination on admission, pre-dose, approximately every 12 hours after dosing till discharge and at follow-up. Adverse event monitoring at admission, pre-dose, 1, 3, 7, 12, 13 and 14 hrs post morning dose on each day (for 28 days) and thereafter at 24, 28, 32, 36, 48, 52, 56, 60, 72, 96 and 120 hours post morning dose of day 28 and at follow-up. Vital Signs will be measured and recordings will be done at screening, on admission, pre dose, 1, 3, 7, 12, 13 and 14 hrs post morning dose on each day and thereafter every 12 hr until discharge and at follow-up and whenever Clinical Investigator/Principal Investigator feels necessary. A 12-Lead ECG will be recorded at screening, pre-dose and 2 hrs, 5 hrs, 12 hrs, and 14 hours after administration of morning dose on 1st, 3rd, 7th, 14th, 21st and 28th day, at discharge and at follow-up. Continuous lead II ECG will be done for first three hours post dose on day 1-3 and upon the judgement of investigator. Haematology, biochemistry, urinalysis will be performed at screening, admission, prior to morning dose on Day 7, 14, 21 and 28, discharge, follow up and at appropriate intervals throughout the study. Ultrasound upper abdomen will be carried out prior to admission and on the day of discharge. Vital signs, 12 lead ECG, safety assessment and adverse event monitoring will be carried out approximately ± 1.5 hours of the scheduled time.

—

Secondary

Measure	Time frame
Pharmacokinetic parameters In plasma for parent and metabolite: Cmax, Tmax, AUC0-t, AUC0-&#61605; , T1/2. In plasma for parent: CL/F and Vd/F. In urine: Total parent drug excreted unchanged (X0) and total demethylated metabolite excreted in urine, renal clearance (CLR) of the parent and metabolite. Pharmacodynamic parameters Total MMP and MMP-9 activity inhibition in plasma and saliva. Timepoint: Blood Sampling: At pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 12.5, 13, 14, 15, 16, 17, 18, 20, 24 hrs post morning dose on Day 1 and Day 28. Additional blood samples will be collected at 48 hrs, 72 hrs, 96 hrs and 120 hrs after morning dose on day 28. In addition, in order to establish steady state, pre-dose blood samples on days 7, 8, 26 and 27 will also be collected. Urine Sampling: Urine samples will be collected from both placebo group and active group at pre-dose and at intervals of 0-4 hrs, 4-8 hrs, 8-12 hrs and 12-24 hrs post morning dose on Day 1 and 28. Additional urine samples will be collected at intervals of 24-48 hrs post-dose after the last morning dose administration. The sampling schedule may be revised and optimized depending on the results of preceding cohorts. Plasma recombinant MMP-9, total MMP and MMP-9 activity inhibition To be assessed at following time points: Day 01: Predose, 2hrs and 11hrs post 1st dose Day 07: 2 hrs, 11hrs post morning dose on day 07 Day 14: 2 hrs, 11hrs post morning dose on day 14 Day 21: 2 hrs, 11hrs post morning dose on day 21 Day 28: 2 hrs, 11hrs post morning dose on day 28	—

Measure

Time frame

Pharmacokinetic parameters In plasma for parent and metabolite: Cmax, Tmax, AUC0-t, AUC0-&#61605; , T1/2. In plasma for parent: CL/F and Vd/F. In urine: Total parent drug excreted unchanged (X0) and total demethylated metabolite excreted in urine, renal clearance (CLR) of the parent and metabolite. Pharmacodynamic parameters Total MMP and MMP-9 activity inhibition in plasma and saliva. Timepoint: Blood Sampling: At pre-dose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 12.5, 13, 14, 15, 16, 17, 18, 20, 24 hrs post morning dose on Day 1 and Day 28. Additional blood samples will be collected at 48 hrs, 72 hrs, 96 hrs and 120 hrs after morning dose on day 28. In addition, in order to establish steady state, pre-dose blood samples on days 7, 8, 26 and 27 will also be collected. Urine Sampling: Urine samples will be collected from both placebo group and active group at pre-dose and at intervals of 0-4 hrs, 4-8 hrs, 8-12 hrs and 12-24 hrs post morning dose on Day 1 and 28. Additional urine samples will be collected at intervals of 24-48 hrs post-dose after the last morning dose administration. The sampling schedule may be revised and optimized depending on the results of preceding cohorts. Plasma recombinant MMP-9, total MMP and MMP-9 activity inhibition To be assessed at following time points: Day 01: Predose, 2hrs and 11hrs post 1st dose Day 07: 2 hrs, 11hrs post morning dose on day 07 Day 14: 2 hrs, 11hrs post morning dose on day 14 Day 21: 2 hrs, 11hrs post morning dose on day 21 Day 28: 2 hrs, 11hrs post morning dose on day 28

—

Countries

India

Contacts

Public ContactMr. Raghu Kochar

vikas.modgill@ranbaxy.com+911244194200

Outcome results