ToxicityPhase 1NCT02778386
Evaluating the Safety and Plasma Levels of N-Methanocarbathymidine (N-MCT) in Normal Patients
A Phase 1 study testing N-Methanocarbathymidine in people with Toxicity, run by N&N Pharmaceuticals Inc. at 1 site in United States.
Trial summary
This Phase I evaluation of N-MCT in normal volunteers requires sequentially increased doses. At each dose level, the safety and pharmacokinetic will be measured. This Phase I trial will have the dose range of N-MCT from 200mg - 1200mg per patient. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Toxicity
- What is being tested?
- N-Methanocarbathymidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subjects must meet all Inclusion Criteria to be included in the study:
- Healthy men and women 18 to 45 years of age, inclusive
- Ability to understand the consent process and study procedures
- Informed consent obtained and signed
- Comprehension of the protocol, as determined by the clinic personnel using a series of questions after explaining the procedures.
- Subjects agree to be available for all study visits.
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- General good health, no current medical illness or clinically significant abnormal physical examination findings as determined by study physician investigators
- Negative past or current history of herpes virus infections, or no current use of antiviral medications for the treatment of herpes virus infections
- Negative serum pregnancy test at screening and a negative serum pregnancy test on the day of admission to the inpatient phase for all female subjects of child bearing potential.
- Negative urine toxicology screen for marijuana, cocaine, opiates, amphetamines, phencyclidine, benzodiazepines, and barbiturates for screening and on the day of admission to the inpatient phase.
- Negative urine toxicology screen for nicotine (Cotinine) for screening and on the day of admission to the inpatient phase.
- Negative breath alcohol screen and agreement not to consume alcohol for the duration of the study.
- Body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than or equal to 29.9 kg/m2 [weight (kg)]/ [height (m)2].
- Agreement by subjects with reproductive potential to use highly effective contraception as described in protocol Section 4.1.1.
- Willingness to avoid strenuous exercise for at least 72 hours prior to initial study drug administration and during the study to Day 7 visit.
- Note: Strenuous physical exercise includes long distance running > 5 km/day, weight lifting, or any physical activity to which the subject is not accustomed.
Who cannot join
- Subjects meeting any of the Exclusion Criteria at Baseline will be excluded from study participation.
- Medical conditions that preclude participation in the study as determined by the study physician investigators.
- Note: Condition that may preclude participation includes:
- 1.1. Vital signs that are outside the ranges in the table below, measured after at least 10 minutes rest:
- Blood Pressure (BP) 90-140/55-90 mmHg Pulse Rate (PR) 50 100 beats/min Tympanic Temperature (T) less than or equal to 37.6ºC Respiration Rate (RR) 12 to 20 breaths/minute
- 1.2. Current diagnosis of pulmonary disease 1.3. Current diagnosis of asthma, which has required use of asthma medications within the past year 1.4. History of or current diagnosis of diabetes mellitus 1.5. Autoimmune disorder, such as systemic lupus erythematosus, Wegener's granulomatosis, rheumatoid arthritis 1.6. History of malignancy except low-grade skin cancer (i.e., basal cell carcinoma which has been surgically cured) 1.7. Chronic renal, hepatic, or pulmonary disease or gastrointestinal tract condition that could interfere with the absorption of the study drug (e.g., surgical resection of significant proportions of the stomach or bowel, gastric bypass, gastric banding, cholecystectomy, irritable bowel syndrome, inflammatory bowel disease) 1.8. History of cardiac abnormalities including Wolff-Parkinson-White syndrome, dysrhythmias, or coronary artery disease 1.9. History of prolonged QT interval
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- Clinically significant abnormal electrocardiogram (ECG) at screening in the judgment of the investigator.
- Screening laboratory values outside the acceptable low and upper limits unless deemed NCS by the principal investigator or sub-investigator.
- Positive serology results for Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) or human immunodeficiency virus (HIV) antibodies
- Febrile illness with temperature documented >38°C within 7 days of dosing
- Pregnancy or breastfeeding
- Known hypersensitivity or allergic reaction(s) to study drug components, including ingredients present in the formulation and/or to other nucleoside analogue antiviral drugs.
- Have consumed any prohibited products or undergone any prohibited procedure listed in Table 3 within the indicated time frame.
- Lack of ability to fully understand the informed consent. This will be determined by the recruiter/interviewer after explaining the consent and observing the subject reading the consent.
- Use of any form of tobacco, including cigarette smoking, pipe smoking, oral tobacco, for 30 days before screening and for the duration of the study.
- Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety.
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
About this study
Official title: Phase I Trial to Assess the Safety and Pharmacokinetics of a Single Ascending Dose (SAD) of N-Methanocarbathymidine (N-MCT) in Normal Volunteers
This Phase I evaluation of N-MCT in normal volunteers requires sequentially increased doses. At each dose level, the safety and pharmacokinetic will be measured. This Phase I trial will have the dose range of N-MCT from 200mg - 1200mg per patient.
Read the detailed description
This is a Phase 1 trial evaluating the safety and pharmacokinetics of N-MCT administered orally as a single ascending dose. Healthy male and female (non-pregnant, non-lactating) subjects ages 18-45, will be consented and allowed to participate in the study if upon screening they meet the inclusion / exclusion criteria.
Subjects will be enrolled into one of four cohort groups sequentially. Each of the six subjects in each group will receive doses sequentially within 48 hours between each dose increase (ie, the second subject in a group will not receive a dose until 48 hours after the first subject received a dose).
Cohort 1 (6 subjects, male \& female) will receive 200 mg, Cohort 2 (6 subjects, male \& female) will receive 400 mg, Cohort 3 (8 subjects, males and females, 2 placebo, 6 treated) will receive 800 mg and Cohort 4 (8 subjects, males and females, 2 placebo, 6 treated) will receive 1200 mg of N-MCT.
Each cohort will be completed and the safety data evaluated prior to initiating the next cohort. All subjects will have plasma and urine samples evaluated for N-MCT.
The PI of the protocol and the IDMC will review safety data (AEs), safety labs, vital signs, and findings through Day 7 for Cohort 1 before enrolling subjects in Cohort 2. Cohort 2 data through Day 7 will be reviewed accordingly by the PI and IDMC before enrolling subjects in Cohort 3. Cohort 3 data through Day 7 will be reviewed by the PI and the IDMC before enrolling subjects in Cohort 4.
However, prior to dose escalation to a new cohort as described above, GHUCCTS IRB will review and approve, in expedited review, the IDMC report upon which the decision to escalate the dose to a new cohort is based.
- Conditions
- Toxicity
- Being tested
- N-Methanocarbathymidine, Placebo Capsule
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-MethanocarbathymidineDrug
Also called N-MCT, NN-001
Patients will receive 200 mg, 400 mg, 800 mg or 1200 mg of N-Methanocarbathymidine administered orally on day 1 after subject's full screen for each cohort. Each dose will be completely evaluated for safety and pharmacokinetics. The doses of each cohort will be given after complete evaluation of the preceding cohort for any sign of toxicity. In the absence of no observed toxicity, the next cohort will be started in the normal subjects.
Placebo CapsuleOther
Also called Placebo
Two patients in Cohort 3 \& 4 will receive placebo capsules which is mannitol filled into size 0 capsules.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 6 subjects, male \& female will receive one dose each of 200 mg of N-Methanocarbathymidine orally in capsules. Each subject will be evaluated for any clinical signs of any toxicity. Receives: Drug: N-Methanocarbathymidine |
| Cohort 2 | Experimental | 6 subjects, male \& female will receive one dose each of 400 mg of N-Methanocarbathymidine orally in capsules. Each subject will be evaluated for any clinical signs of any toxicity. Receives: Drug: N-Methanocarbathymidine |
| Cohort 3 | Experimental | 8 subjects, males and females, 6 subjects will receive one dose each 800 mg of N-Methanocarbathymidine orally in capsules and 2 will receive a placebo capsule. Each subject will be evaluated for any clinical signs of any toxicity. Receives: Drug: N-Methanocarbathymidine; Other: Placebo Capsule |
| Cohort 4 | Experimental | 8 subjects, males and females, 6 subjects will receive one dose each 1200 mg of N-Methanocarbathymidine orally in capsules and 2 will receive a placebo capsule. Each subject will be evaluated for any clinical signs of any toxicity. Receives: Drug: N-Methanocarbathymidine; Other: Placebo Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Safety and Tolerability of N-MCT Evaluated By The Sequential Review of Reported Adverse Events (AEs) and Changes from Baseline in Findings on Physical Examination, Vital Sign Measurements, and Safety Laboratory Tests
The type, incidence, severity and relatedness to study drug of adverse events (AEs), and of abnormal findings on physical examination, vital sign measurements, and of safety laboratory tests (hematology, biochemistry, urinalysis) throughout the study period.
Measured: Day 1- Day 7
Secondary outcomes (2)
Plasma Concentrations of N-MCT Measured Before and at Multiple Time Points After Oral administration
Plasma levels of N-MCT will be measured before and at multiple time points after the oral administration.
Plasma drug concentrations will be obtained at the following time points: pre-dose (0.000), 0.250, 0.500,0.750, 1.000, 1.500, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 12.000, 24.000 and 48.000 hours.
Measured: Pre-Dose (0.000), 0.250, 0.500,0.750, 1.000, 1.500, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 12.000, 24.000 and 48.000 hours
Urine Concentrations of N-MCT Measured Before and at Multiple Time Points
Urine concentrations of N-MCT will be measured before and at multiple time points after the oral administration. Pooled urine samples for the measurement of N-MCT concentration will be collected over the following intervals: 0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose.
Measured: 0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2016 (estimated)
- Study startApr 2016
- Primary completionDec 2016 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ToxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- N&N Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Aquilur Rahman, PhD, Study director, N&N Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02778386
- Sponsor's protocol ID
- N-MCT 329-15
- Status last verified
- Sep 2016
- First submitted
- 27 Apr 2016
- Last updated
- 22 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial to Assess the Safety and Pharmacokinetics of a Single Ascending Dose (SAD) of N-Methanocarbathymidine (N-MCT) in Normal Volunteers
- ClinicalTrials.gov ID
- NCT02778386
- Acronym / sponsor ID
- N-MCT 329-15
- Conditions
- Toxicity
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- N&N Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2016
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 19 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase I evaluation of N-MCT in normal volunteers requires sequentially increased doses. At each dose level, the safety and pharmacokinetic will be measured. This Phase I trial will have the dose range of N-MCT from 200mg - 1200mg per patient.
Detailed description
This is a Phase 1 trial evaluating the safety and pharmacokinetics of N-MCT administered orally as a single ascending dose. Healthy male and female (non-pregnant, non-lactating) subjects ages 18-45, will be consented and allowed to participate in the study if upon screening they meet the inclusion / exclusion criteria.
Subjects will be enrolled into one of four cohort groups sequentially. Each of the six subjects in each group will receive doses sequentially within 48 hours between each dose increase (ie, the second subject in a group will not receive a dose until 48 hours after the first subject received a dose).
Cohort 1 (6 subjects, male \& female) will receive 200 mg, Cohort 2 (6 subjects, male \& female) will receive 400 mg, Cohort 3 (8 subjects, males and females, 2 placebo, 6 treated) will receive 800 mg and Cohort 4 (8 subjects, males and females, 2 placebo, 6 treated) will receive 1200 mg of N-MCT.
Each cohort will be completed and the safety data evaluated prior to initiating the next cohort. All subjects will have plasma and urine samples evaluated for N-MCT.
The PI of the protocol and the IDMC will review safety data (AEs), safety labs, vital signs, and findings through Day 7 for Cohort 1 before enrolling subjects in Cohort 2. Cohort 2 data through Day 7 will be reviewed accordingly by the PI and IDMC before enrolling subjects in Cohort 3. Cohort 3 data through Day 7 will be reviewed by the PI and the IDMC before enrolling subjects in Cohort 4.
However, prior to dose escalation to a new cohort as described above, GHUCCTS IRB will review and approve, in expedited review, the IDMC report upon which the decision to escalate the dose to a new cohort is based.
Study design
- Primary purpose
- Health services research
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: N-Methanocarbathymidine6 subjects, male \& female will receive one dose each of 200 mg of N-Methanocarbathymidine orally in capsules. Each subject will be evaluated for any clinical signs of any toxicity. |
| Cohort 2 | Experimental | Drug: N-Methanocarbathymidine6 subjects, male \& female will receive one dose each of 400 mg of N-Methanocarbathymidine orally in capsules. Each subject will be evaluated for any clinical signs of any toxicity. |
| Cohort 3 | Experimental | Drug: N-Methanocarbathymidine, Other: Placebo Capsule8 subjects, males and females, 6 subjects will receive one dose each 800 mg of N-Methanocarbathymidine orally in capsules and 2 will receive a placebo capsule. Each subject will be evaluated for any clinical signs of any toxicity. |
| Cohort 4 | Experimental | Drug: N-Methanocarbathymidine, Other: Placebo Capsule8 subjects, males and females, 6 subjects will receive one dose each 1200 mg of N-Methanocarbathymidine orally in capsules and 2 will receive a placebo capsule. Each subject will be evaluated for any clinical signs of any toxicity. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (16 listed)
- Healthy men and women 18 to 45 years of age, inclusive
- Ability to understand the consent process and study procedures
- Informed consent obtained and signed
- Comprehension of the protocol, as determined by the clinic personnel using a series of questions after explaining the procedures.
- Subjects agree to be available for all study visits.
Key exclusion criteria (16 listed)
- Subjects meeting any of the Exclusion Criteria at Baseline will be excluded from study participation.
- 1.1. Vital signs that are outside the ranges in the table below, measured after at least 10 minutes rest:
- Blood Pressure (BP) 90-140/55-90 mmHg Pulse Rate (PR) 50 100 beats/min Tympanic Temperature (T) less than or equal to 37.6ºC Respiration Rate (RR) 12 to 20 breaths/minute
- 1.2. Current diagnosis of pulmonary disease 1.3. Current diagnosis of asthma, which has required use of asthma medications within the past year 1.4. History of or current diagnosis of diabetes mellitus 1.5. Autoimmune disorder, such as systemic lupus erythematosus, Wegener's granulomatosis, rheumatoid arthritis 1.6. History of malignancy except low-grade skin cancer (i.e., basal cell carcinoma which has been surgically cured) 1.7. Chronic renal, hepatic, or pulmonary disease or gastrointestinal tract condition that could interfere with the absorption of the study drug (e.g., surgical resection of significant proportions of the stomach or bowel, gastric bypass, gastric banding, cholecystectomy, irritable bowel syndrome, inflammatory bowel disease) 1.8. History of cardiac abnormalities including Wolff-Parkinson-White syndrome, dysrhythmias, or coronary artery disease 1.9. History of prolonged QT interval
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-MethanocarbathymidineAlso: N-MCT, NN-001Patients will receive 200 mg, 400 mg, 800 mg or 1200 mg of N-Methanocarbathymidine administered orally on day 1 after subject's full screen for each cohort. Each dose will be completely evaluated for safety and pharmacokinetics. The doses of each cohort will be given after complete evaluation of the preceding cohort for any sign of toxicity. In the absence of no observed toxicity, the next cohort will be started in the normal subjects. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| Placebo CapsuleAlso: PlaceboTwo patients in Cohort 3 \& 4 will receive placebo capsules which is mannitol filled into size 0 capsules. | Other | Cohort 3, Cohort 4 |
Primary outcome
The Safety and Tolerability of N-MCT Evaluated By The Sequential Review of Reported Adverse Events (AEs) and Changes from Baseline in Findings on Physical Examination, Vital Sign Measurements, and Safety Laboratory Tests
Time frame: Day 1- Day 7
The type, incidence, severity and relatedness to study drug of adverse events (AEs), and of abnormal findings on physical examination, vital sign measurements, and of safety laboratory tests (hematology, biochemistry, urinalysis) throughout the study period.
2 secondary outcomes
Plasma Concentrations of N-MCT Measured Before and at Multiple Time Points After Oral administration
Time frame: Pre-Dose (0.000), 0.250, 0.500,0.750, 1.000, 1.500, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 12.000, 24.000 and 48.000 hours
Urine Concentrations of N-MCT Measured Before and at Multiple Time Points
Time frame: 0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aquilur Rahman, PhD study director
N&N Pharmaceuticals Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N-Methanocarbathymidine in people with Toxicity, run by N&N Pharmaceuticals Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Safety and Tolerability of N-MCT Evaluated By The Sequential Review of Reported Adverse Events (AEs) and Changes from Baseline in Findings on Physical Examination, Vital Sign Measurements, and Safety Laboratory Tests (time frame: Day 1- Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2016.