Arteriosclerosis, stenosis, vascular insufficiency and necrosis Circulatory System
Conditions
Interventions
SAD part:
From groups 1 to 7: an ascending dose of 1 mg to 400 mg INS-3001 or placebo.
MAD part:
From groups 1 to 4: dose of 25 mg to 200 mg INS-3001 or placebo.
Sponsors
Vifor (International) Inc.
Eligibility
Sex/Gender
All
Age
21 Years to 60 Years
Inclusion criteria
Inclusion criteria: SAD part: A1. Age: 21 to 60 years, inclusive, at screening. A2. Body mass index (BMI): 18.0 to 30.0 kg/m2, inclusive, at screening. A3. Being male or female; females must be of non-childbearing potential (ie, surgically sterilized [ie, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy], physiologically incapable of becoming pregnant, or at least 1 year postmenopausal [amenorrhea duration of >=12 consecutive months]). A4. Females must not be pregnant or lactating; nonpregnancy will be confirmed for all females by a serum pregnancy test conducted at screening, at admission, and at follow-up. A5. Male subjects, if not surgically sterilized (i.e., vasectomized), must agree to use adequate contraception when having intercourse with a female sexual partner of childbearing potential and to not donate sperm from admission to the clinical site until 90 days after the follow-up visit. A6. In good physical and mental health on the basis of medical history, physical examination, and routine laboratory measurements (ie, without major or clinically relevant pathology), as judged by the Investigator. A7. Normal arterial blood pressure (systolic blood pressure of 90 to 140 mmHg, inclusive, and diastolic blood pressure of 45 to 90 mmHg, inclusive) and pulse rate (40 to 100 beats per minute, inclusive). Measurement of blood pressure and/or pulse may be repeated if in the judgment of the Investigator there is a reason to believe the initial result is inaccurate (eg, white coat hypertension). A8. Computerized (12-lead) ECG recording without signs of clinically relevant pathology, as judged by the Investigator. The ECG may be repeated if in the judgment of the Investigator there is a reason to believe the initial result is inaccurate. A9. Willing and able to abstain from alcohol for 72 hours (3 days) prior to screening and from 72 hours prior to study drug administration until the last PK blood sampling. A10. Willing and able to abstain from methylxanthine-containing beverages (coffee, tea, cola, or other caffeinated beverages) from 48 hours (2 days) prior to study drug administration until the last PK blood sampling. A11. Willing and able to abstain from herbal medications or dietary supplements (eg, St. John*s Wort or ginkgo biloba), vitamin preparations, grapefruit or grapefruit juice, or Seville oranges from 14 days prior to administration of the study drug until follow-up. A12. Willing and able to understand and comply with the protocol requirements and instructions and likely to complete the study as planned. A13. Willing and able to read, understand, and sign the ICF. MAD part: B1. Age : >55 years at screening. B2. BMI: 18.0 to 35.0 kg/m2, inclusive, at screening. B3. Being male or female; females must be of nonchildbearing potential (ie, surgically sterilized [ie, hysterectomy, bilateral salpingectomy, or bilateral oophorectomy], physiologically incapable of becoming pregnant, or at least 1 year postmenopausal [amenorrhea duration of >=12 consecutive months and confirmed by a follicle-stimulating hormone {FSH} test at screening]). B4. Females must not be pregnant or lactating; nonpregnancy will be confirmed for all females by a serum or urine pregnancy test conducted at screening, at first admission, and at follow-up. B5. Male subjects, if not surgically sterilized (i.e., vasectomized), must agree to use adequate contraception when having intercourse with a female sexual partner of childbearing potential and to not donate sperm from
Exclusion criteria
Exclusion criteria: SAD part: A1. Treatment with prescription medications within 14 days prior to study drug administration. An exception is made for vaccines against SARS-CoV-2, which will be allowed but must be discussed with the Investigator to mitigate against any interruptions to trial-related procedures and assessments. Potential subjects should only stop any prescribed medication at the direction of a physician. A2. Treatment with nonprescription medications within 14 days prior to study drug administration. An exception is made for paracetamol, which is allowed up to admission to the clinical site. Potential subjects should consult a physician before stopping any regular treatment with nonprescription medication. A3. Using tobacco products within 3 months prior to study drug administration. A4. History of alcohol or drug abuse or addiction within 2 years prior to study drug administration. A5. Regular consumption of more than 14 units of alcohol per week for females and more than 21 units of alcohol per week for males (1 unit equals 250 mL of beer, 100 mL of wine, or 35 mL of spirits). A6. Regular consumption of more than 8 cups of methylxanthine-containing beverages (coffee, tea, cola, or other caffeinated beverage) per day (1 cup equals 250 mL). A7. Participation in a clinical study involving administration of an investigational or a marketed drug within 3 months prior to screening. Participation in more than 4 other drug studies in the 12 months prior to study drug administration in the current study. A8. Blood donation or a significant loss of blood (>450 mL) within 60 days prior to study drug administration or donation of more than 1 unit of plasma within 7 days prior to screening. A9. Employee of PRA Health Sciences (PRA) or the Sponsor. A10. History of any illness or condition that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk when administering the study drug to the subject. A11. Positive drug or alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], cannabinoids, barbiturates, benzodiazepines, gamma hydroxybutyric acid, tricyclic antidepressants, cotinine, or alcohol) at screening or at admission to the clinical site. A12. Previous participation in the current study. A13. Positive result at screening for any of the following infectious disease tests: hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, or human immunodeficiency virus (HIV) 1 and 2 antibodies. A14. Positive PCR test for SARS CoV-2 at admission to the clinical site. A15. Unsuitable veins for infusion or blood sampling. A16. History of relevant drug and/or food allergies. A17. Illness within 5 days prior to study drug administration (*illness* is defined as an acute [serious or non-serious] condition [eg, the flu or the common cold]). MAD part: B1. Rheumatic or unicuspid aortic valves. B2. Patients with aortic sclerosis, mild or severe aortic stenosis, or absence of aortic valve calcification (ie, parameters outside the limits defined in the inclusion criteria). B3. Severe mitral or aortic regurgitation. B4. Severe mitral stenosis. B5. History of aortic valve replacement. B6. Aortic valve replacement or repair scheduled or anticipated during the study period. B7. Left ventricular ejection fraction 480 msec (in case of a left bundle branch block [LBBB], the QT-interval can be corrected for LBBB by the formula QTLBBB - [0.86 * QRSLBBB 71]; for paced rh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants who experienced a treatment-emergent adverse event (TEAE). A TEAE was defined as any event not present prior to the first administration of the study drug or any event already present that worsened in either severity or frequency following exposure to the study drug. Any clinically significant observations in the results of clinical laboratory, vital signs, 12-lead electrocardiograms (ECGs), continuous cardiac monitoring (telemetry; SAD part only), physical examinations, or injection site assessments, as determined by the Investigator, will be recorded as TEAEs. SAD: Day 1 to Day 24; MAD: Day 1 to Day 37. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. SAD Only: Serum concentration of INS-3001. Blood samples of 4 ml will be taken via an indwelling intravenous (IV) catheter or by direct venipuncture into heparin tubes. For calculation of descriptive statistics, below quantification level (BQL) values are set 1/2 lower limit of quantification (LLOQ) according to the statistical analysis plan (SAP). Day 1: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose. 2. MAD Only: Serum concentration of INS-3001. Blood samples of 4 ml will be taken via an indwelling IV catheter or by direct venipuncture into heparin tubes. For calculation of descriptive statistics, BQL values are set 1/2 LLOQ according to the SAP. Day 1: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose; Days 2, 3 and 8: Pre-dose; Day 14: Pre- dose and 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose. 3. MAD Only: Trough plasma concentration (Ctrough) of INS-3001. Blood samples of 4 ml will be taken via an indwelling IV catheter or by direct venipuncture into heparin tubes. Ctrough was defined as the pre-dose plasma concentration on Days 2, 3, 8 and 14. Days 2, 3, 8, and 14: Pre-dose. 4. Maximum plasma concentration (Cmax) of INS-3001. Blood samples of 4 ml will be taken via an indwelling IV catheter or by direct venipuncture into heparin tubes. Cmax was defined as the observed peak analyte concentration obtained directly from the experimental data without interpolation, expressed in concentration units. SAD - Day 1: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours post-dose. MAD - Day 1 and Day 14: Pre-dose and 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 168 (Day 14 only) hours post-dose. 5. Time to Cmax (Tmax) of INS-3001. Blood samples of 4 ml will be taken via an indwelling IV catheter or by direct venipuncture into heparin tubes. Tmax was defined as the first observed time to reach peak analyte concentration obtained directly from the experimental data withou | — |
Countries
Netherlands, Scotland, United Kingdom
Outcome results
None listed