Primary objective:To evaluate the single- and multiple-dose safety and pharmacokinetics of CNM-Au8 upon oral administration of CNM-Au8 to healthy adult male and female subjects.Secondary objective:Exploreing the immune-modulating effects of CNM-Au8…
ID
Source
Brief title
Condition
- Demyelinating disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacokinetic endpoints:
SAD Phase: maximum observed plasma concentration (Cmax), time to Cmax (Tmax),
the area under the plasma concentration versus time curve from time 0 (predose)
to time infinity (AUCinf), AUC from time 0 to time of last measurable plasma
concentration (AUClast), the percentage of the AUC that is extrapolated
beyond the last measurable concentration (AUCext), the elimination rate
constant (*z), the apparent systemic clearance (CL/F), mean residence time
(MRT), apparent volume of distribution, terminal phase (Vz/F), and
terminal-phase half-life (t*) will be calculated using non-compartmental
analyses and PK modeling.
MAD Phase: pharmacokinetic parameters such as the maximum observed plasma
concentration (Cmax), time to Cmax (Tmax), Cmin, and the area under the plasma
concentration versus time curve from time 0 (predose) to the end of the 24-hour
dosing interval (AUC*) will be calculated on Days 1, 7, 14 and 21. The apparent
systemic clearance (CL/F) will be calculated from the steady-state
concentration-time profile. Other parameters such as the accumulation ratio
(RAcc) elimination rate constant (*z), mean residence time (MRT), apparent
volume of distribution, terminal phase (Vz/F), and terminal-phase half-life
(t*) will be calculated when appropriate using non-compartmental analyses and
PK modeling.
Safety endpoints are as follows:
• Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse
Events
(SAEs) grouped by body system
• Changes from Baseline in clinical laboratory, urinalysis, vital
signs, and ECG
parameters to discharge and Follow-Up
• Changes from pre-dose physical exam findings to Follow-Up
Secondary outcome
Pharmacodynamic endpointss
• TLR9-induced cytokines
• Other related cytokines
Background summary
Gold complexes have been widely used in the treatment of rheumatoid arthritis
for over 80 years. The mechanism of action of gold salt compounds is not well
understood, but gold appears to accumulate slowly in the body to gradually
reduce inflammation and slow the progression of rheumatoid arthritis.
Unfortunately, clinical use of traditional gold compounds is compromised by
multiple forms of toxicity, commonly including pruritus, dermatitis,
stomatitis, diarrhea, and proteinuria, and, less frequently, hematological.
The role of gold itself in the pattern of toxicity in gold salts is unclear,
but it is hypothesized that at least some complications arise from the related
formulations rather than from the gold itself raising the possibility that a
cleaner form of gold delivery might incur fewer complications. CNM-Au8 consists
of clean-surface gold nanocrystals, and may therefore cause less of the
side-effect. Preclinical studies showed gold stimulated remyelination. In the
future, CNM-Au8 would possibly be a therapeutic option for diseases like
neuromyelitis optica.
Study objective
Primary objective:
To evaluate the single- and multiple-dose safety and pharmacokinetics of
CNM-Au8 upon oral administration of CNM-Au8 to healthy adult male and female
subjects.
Secondary objective:
Exploreing the immune-modulating effects of CNM-Au8 and qualifying a bioassay
for demonstration of CNM-Au8*s anti-inflammatory effects.
Study design
A phase 1 randomized, placebo-controlled, double-blind, first-in-human,
single-ascending dose (SAD) and multiple-ascending dose (MAD) Study
Study burden and risks
This is the first time that CNM-Au8 will be administered to human volunteers.
Preclinical trials shows that long-term use of the compound could cause a
decrease in platelets. Other preclinical data show that gold accumulated a
little bit in the kidneys, without interfering with the renal function.
Other compounds with gold (like auranofin) have these side-effects: nausea,
diarrhea, decrease in appetite, abdominal cramps, pruritus.
Venapuncture: Inserting a catheter for taking blood for testing may cause pain
and discomfort such as bleeding, bruising, dizziness, fainting, inflammation of
the vein and infection.
We consider the burden and the risks described above to be minimal. Especially
with the low starting dose and the step-wise dose increase minimize the risk is
low.
3165 East Millrock Drive, Suite 325
Salt Lake City 84121
US
3165 East Millrock Drive, Suite 325
Salt Lake City 84121
US
Listed location countries
Age
Inclusion criteria
1. An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.
2. Is between the ages of 18 and 45 years, inclusive.
3. Females will be non-pregnant, non-lactating, and either post-menopausal for at least 1 year, surgically sterile (e.g., tubal ligation, hysterectomy) for at least 90 days, or agree, from the time of signing the informed consent or 14 days prior to check-in until 30 90 days after Study Completion/Discharge, to use two forms of contraception.
4. Has a body mass index (BMI) between 18 and 34 kg/m2.
5. All laboratory values at screening fall within normal range or are evaluated as not clinically significant (NCS) by the Investigator if outside normal range.
6. Has no clinically significant abnormal findings during pre-dose physical examination or
Screening and Baseline vital signs or ECG.
7. Has not consumed and agrees to abstain from taking any dietary supplements or non- prescription drugs (except as authorized by the Investigator AND Medical Monitor) for 3 days prior to CRU admission through Follow-Up.
8. Has not consumed and agrees to abstain from taking any prescription drugs (except as authorized by the Investigator AND Medical Monitor) during the 14 days prior to CRU admission through Follow-Up.
9. Has not consumed alcohol-containing beverages for starting 3 days prior to CRU admission and agrees not to consume alcohol through Follow-Up.
10. Has not consumed grapefruit or grapefruit juice within the 14 days prior to CRU
admission and agrees not to consume grapefruit or grapefruit juice through Follow-Up.
11. Has not used tobacco- and nicotine-containing products within 60 days prior to the CRU admission and agrees to abstain from using tobacco- and nicotine-containing products through Follow-Up.
12. Has the ability to understand the requirements of the study and is willing to comply with all study procedures.
Exclusion criteria
1. Has a history of illicit drug abuse in the past year or current evidence of such abuse in the opinion of the Investigator.
2. Has positive findings on urine drug screen.
3. Is positive for human immunodeficiency virus (HIV), hepatitis B and/or hepatitis C on screening assessments.
4. Is pregnant or lactating.
5. Has clinically significant medical or psychiatric history that, in the Investigator*s judgment, would compromise the subject*s safety or the collection of data.
6. Has donated plasma within 7 days of CRU admission.
7. Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening.
8. Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000669-29-NL |
| CCMO | NL52617.056.15 |