A Phase I/Ib Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of DSM265 in Healthy Subjects and to Assess the Antimalarial Activity of DSM265 in Healthy Subjects with an Induced Blood Stage Plasmodium falciparum Infection.PART 1.
- Conditions
- Infection - Other infectious diseasesMalaria
- Registration Number
- ACTRN12613000522718
- Lead Sponsor
- CPR Pharma Services
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 73
1. Written informed consent must be obtained before any assessment is performed.
2. Healthy male and female (of non-childbearing potential) subjects age 18 to 55 years in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
a. Women are considered post-menopausal and not of child bearing potential if they have had at least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels at the local laboratory levels for post-menopause; or have had surgical bilateral oophorectomy or bilateral salpingectomy (with or without hysterectomy) at least six months ago. Women on oral contraceptives are to be excluded from the study, also women who have had a tubal ligation.
3. At screening and baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three (3) minutes and again when required after three (3) minutes in the standing position. Investigators can be guided by the following ranges:
a. oral body temperature between 35.0-37.5 degrees celcius
b. systolic blood pressure, 90-140 mm Hg
c. diastolic blood pressure, 50-90 mm Hg
d. pulse rate, 40-90 bpm
4. When blood pressure and pulse are taken after at least 3 minutes standing, there should be no more than a 20 mm Hg drop in systolic or 10 mm Hg drop in diastolic blood pressure and increase in heart rate (>20 bpm) (compared to the sitting results) associated with clinical manifestation of postural hypotension. Any subject exhibiting clinical manifestations of postural hypotension should be excluded.
5. Must have haematology, clinical chemistry and urinalysis results at screening that are within the reference range or, if outside the range, not clinically significant as judged by the investigator and confirmed and agreed by the medical monitor; aspartate aminotransferase (AST), ALT and bilirubin must be within the reference range at screening
6. Subjects must:
a. Weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18-30 kg/m2.
b. Be able to communicate well with the investigator, to understand and comply with the requirements of the study.
7. Good peripheral venous access
1. Known hypersensitivity to any of the study drugs.
2. Use of other investigational drugs at the time of enrolment, or within 30 days or 5 half-lives of enrolment, whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
4. A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at Screening or Baseline:
a. PR >210 msec
b. QRS complex >120 msec
c. QTcF >450 msec or shortened QTcF less than 340 msec or a family history of long QT syndrome or sudden death.
d. Second or third degree atrioventricular block.
e. Incomplete, full or intermittent bundle branch block.
f. Abnormal T wave morphology.
5. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
6. Pregnant or nursing (lactating) women.
7. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation
precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means.
8. Fertile males, defined as all males physiologically capable of conceiving offspring UNLESS the subject agrees to comply with two highly effective contraceptive methods comprising a barrier method (condom) for the entire duration of the study, and twelve weeks following the last study drug administration. Vasectomised males to use a condom for the entire study and 12 weeks following drug administration.
9. Smokers (use of tobacco products in the previous 3 months). Urine cotinine levels will be measured during screening and at each baseline for all subjects. Smokers will be defined as any subject who reports tobacco use and/or who has a urine cotinine greater than or equal to 500 ng/mL. For light smokers (defined as less than 5 cigarettes per day) to pass the cotinine test, smoking should be stopped at least 24 hours prior to reporting to the centre (i.e., Day -2, early morning). Smoking will not be allowed during the study.
10. Use of any prescription drugs, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing (note that diazepam interferes with the analysis of DSM265 and should not have been used for 8 weeks prior to initial dosing). If needed, (i.e. an incidental and limited need) paracetamol is acceptable up 4 g/day, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF.
11. Intake of grapefruit, grapefruit juice or other products containing grapefruit within 14 days of the first drug administration.
12. Excessive intake of caffeine drinks or energy drinks within 48 hours before admission defined as more than three 8 oz. cups of coffee a day, equivalent to roughly 250 mg of caffeine. Defined as 1 (6oz) cup of coffee; 2 cans of cola; 1 (12oz) cup of tea; 3oz milk chocolate.
13. Consumption of broccoli, caviar, sardines, liver, heart and kidneys and yeast supplements one day prior to dosing and throughout the dosing phase. tomatoes and vegemite to be avoided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The purpose of the study is to determine the maximum oral dose of DSM265 that can be tolerated by healthy adults.<br><br>This will be determined by the PK results.[PK collections at Day 1 Pre-dose, Day 1 0.5, 1, 2, 4, 6, 8, 12 hrs post dose, Days 2, 3, 5, 7, 10, 14, and 21.<br><br>];To derive the pharmacokinetic properties of DSM265 in humans (including food effect).<br><br>This will be determined by the PK results.[PK collections at Day 1 Pre-dose, Day 1 0.5, 1, 2, 4, 6, 8, 12 hrs post dose, Days 2, 3, 5, 7, 10, 14, and 21.<br><br>]
- Secondary Outcome Measures
Name Time Method il[Nil]