Major Depressive DisorderPhase 1NCT04623034
Evaluation of the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine
A Phase 1 study testing Ademetionine in people with Major Depressive Disorder, run by MSI Methylation Sciences, Inc..
Trial summary
This study was a pharmacokinetic and safety evaluation of the S-adenosylmethionine formulation MSI-195, and a commercial comparator. The study was broken into two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. Read more about this study
- Who is it for?
- Ages 21 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Ademetionine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- No sites listed yet
- Study dates
- 17 Apr 2013to 8 Jun 2013
- 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 21 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Volunteers meeting all of the following criteria will be considered for enrollment in the study:
- Availability for the entire study period
- Motivated volunteer and absence of intellectual problems likely to limit the validity of consent to participate in the study or the compliance with protocol requirements; ability to cooperate adequately; ability to understand and observe the instructions of the physician or designee
- Male or female volunteer (Male only for Stage 1 - Cohort 1)
- A female volunteer must meet one of the following criteria:
- Participant is of childbearing potential and agrees to use one of the accepted contraceptive regimens throughout her entire participation in the study. An acceptable method of contraception includes one of the following:
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- Abstinence from heterosexual intercourse
- Systemic contraceptives (birth control pills, injectable/implantable /insertable hormonal birth control products, transdermal patch)
- Intrauterine device
- Condom with spermicide or
- Participant is of non-childbearing potential, defined as a female who had had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
- Volunteer aged of at least 21 years but not older than 55 years
- Volunteer with a body mass index (BMI) greater than or equal to 18.50 and below 30.00 kg/m2
- Non- or ex smokers; an ex-smoker being defined as someone who completely stopped smoking for at least 6 months before day 1 of this study.
- Clinical laboratory values within the laboratory's stated normal range; if not within this range, they must be without any clinical significance
- Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination and/or clinical laboratory evaluations (hematology, general biochemistry, ECG and urines)
- Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the volunteer
- The informed consent form must be signed by all volunteers, prior to their participation in the study.
Who cannot join
- Volunteers presenting any of the following will not be included in the study:
- Females who are pregnant or are lactating
- History of significant hypersensitivity to S-Adenosylmethionine or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
- Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
- History of significant gastrointestinal, liver or kidney disease that may affect drug bioavailability
- Presence of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
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- Suicidal tendency, history of or disposition to seizures, state of confusion, clinically relevant psychiatric diseases
- Presence of out-of-range cardiac interval (PR < 110 msec, PR > 220 msec, QRS < 60 msec, QRS >119 msec, QTc > 450 msec for males and > 460 msec for females) on the screening ECG or other clinically significant ECG abnormalities
- Presence or history of bipolar disorder
- Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
- Any clinically significant illness in the previous 28 days before day 1 of this study
- Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study
- Any history of tuberculosis and/or prophylaxis for tuberculosis
- Positive urine screening of alcohol and/or drugs of abuse
- Positive results to HIV Ag/Ac Combo, HBsAg (B) (hepatitis B) or anti-HCV (C) tests
- Females who are pregnant according to a positive serum pregnancy test
- Volunteers who took an Investigational Product (in another clinical trial) or donated 50 mL or more of blood in the previous 28 days before day 1 of this study
- Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the previous 56 days before day 1 of this study
- No subjects will be allowed to enroll in this study more than once (i.e. if the study is conducted with more than 1 group).
About this study
Official title: A Phase 1, Two Stage, Open Label, Randomized, Single Dose, Comparative Study to Evaluate the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine Product in Healthy Volunteers
This study was a pharmacokinetic and safety evaluation of the S-adenosylmethionine formulation MSI-195, and a commercial comparator. The study was broken into two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. The second stage was a single dose evaluation, targeting 26 male and female volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed by a food effect study on MSI-195. Plasma samples were collected and assayed for S-adenosylmethionine. Pharmacokinetic parameters were calculated using that data.
Read the detailed description
The study was focussed on the safety and pharmacokinetic evaluation of MSI-195; a novel patented formulation of S-adenosylmethionine. MSI-195 is a 400 mg dosage strength, tablet formulation comprising a core tablet, a seal coat and an enteric coat. The commercial comparator is SAM-e CompleteTM, manufactured by Pharmavite under the NatureMadeTM brand.
This study consisting of two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. The second stage was a more comprehensive single dose evaluation, targeting 26 male and female volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed by a food effect study on MSI-195.
Stage 1 design In each period of this stage of the study, ascending single doses of 400 mg, 800 mg and 1600 mg of MSI-195 was orally administered under fasted conditions, followed by 24 hours of blood draws at periodic intervals for the determination of plasma concentration of S-adenosylmethionine in a repeated-measure design. The drug administrations were separated by a wash-out of 7 calendar days.
Stage 2 design In the first 2 periods of this stage of the study, a single 800 mg dose of MSI-195 and a single 1600 mg dose of commercial comparator were orally administered under fasted conditions, in a 2-way crossover design. During the 3rd period, a single 800 mg dose of MSI-195 was administered under fed conditions to all subjects. The drug administrations were separated by a wash-out of 7 calendar days. For each dosing, subjects had periodic blood draws over a 24 hour period to determine the plasma concentration of S-adenosylmethionine as a function of time.
Male and female volunteers were included in the study. Subjects were in good health as determined by a medical history, complete physical examination (including vital signs), electrocardiogram (ECG), neurological examination and a panel of clinical laboratory tests.
Blood samples were collected and stored frozen until assayed. The samples were assayed for S-adenosylmethionine using a validated HPLC method with MS/MS detection.
For pharmacokinetic assessments, the main absorption and disposition parameters were calculated using a non-compartmental approach with a log-linear terminal phase assumption. The pharmacokinetic parameters of this trial were Cmax, Tmax, AUCT, AUC∞, AUCT/∞, Kel and T½el.
The safety parameters assessed included the occurrence of adverse events, the measurement of clinical laboratory parameters, vital signs, neurological function tests, physical examination and ECG
- Conditions
- Major Depressive Disorder
- Being tested
- Ademetionine
- Keywords
- depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdemetionineDrug
| Study group | Role | What they receive |
|---|---|---|
| 400 mg MSI-195 - SAD | Experimental | 400 mg MSI-195 (within Stage 1, single ascending dose) Receives: Drug: Ademetionine |
| 800 mg MSI-195 - SAD | Experimental | 800 mg MSI-195 (within Stage 1, single ascending dose) Receives: Drug: Ademetionine |
| 1600 mg MSI-195 -SAD | Experimental | 1600 mg MSI-195 (within Stage 1, single ascending dose) Receives: Drug: Ademetionine |
| 800 mg MSI-195 - fasted | Experimental | 800 mg MSI-195 fed (within Stage 2, cross-over comparison) Receives: Drug: Ademetionine |
| 1600 mg SAM-e Complete TM - fasted | Experimental | 1600 mg SAM-e Complete (within Stage 2, cross-over comparison) Receives: Drug: Ademetionine |
| 800 mg MSI-195 - fed | Experimental | 800 mg MSI-195- fed (within Stage 2, fed arm) Receives: Drug: Ademetionine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of treatment-related adverse events (safety and tolerability) as measured by vital signs, ECG, laboratory tests, neurological function tests, and the occurance of adverse events
Incidence and severity of treatment-related adverse events determined by changes from screening (baseline) of findings from physical examination, vital signs, ECG, laboratory tests, neurological function tests, and the occurance of adverse events.
Measured: for 24 hours after dosing
Pharmacokinetics was evaluated by measuring the systemic plasma concentration of ademetionine
plasma concentrations of ademetionine were measured as a function of time using a validated bioanalytical assay
Measured: for 24 hours after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2020
- Study start17 Apr 2013
- Primary completion8 Jun 2013
- Study completion8 Jun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Stage 1 - single ascending dose, Stage 2 - crossover and food effect study
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- MSI Methylation Sciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Algorithme Pharma Inc
- Responsible party
- Sponsor
- Investigators
- Eric Sicard, M.D., Principal investigator, Algorithme Pharma Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04623034
- Sponsor's protocol ID
- MSI-CP.001.02
- Status last verified
- Nov 2020
- First submitted
- 30 Oct 2020
- Last updated
- 10 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cameron BR, Ferreira L, MacDonald ID. Pharmacokinetic study of a novel oral formulation of S-adenosylmethionine (MSI-195) in healthy subjects: dose escalation, food effect and comparison to a commercial nutritional supplement product. BMC Pharmacol Toxicol. 2020 Dec 14;21(1):88. doi: 10.1186/s40360-020-00466-7.
PubMed 33317621
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Two Stage, Open Label, Randomized, Single Dose, Comparative Study to Evaluate the Safety and Pharmacokinetics of MSI-195 to a Commercial S-Adenosylmethionine Product in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04623034
- Acronym / sponsor ID
- MSI-CP.001.02
- Conditions
- Major Depressive Disorder
- Keywords
- depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- MSI Methylation Sciences, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Algorithme Pharma Inc
- Study start
- 17 Apr 2013 (actual)
- Primary completion
- 8 Jun 2013 (actual)
- Study completion
- 8 Jun 2013 (actual)
- First posted
- 10 Nov 2020 (actual)
- 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 study was a pharmacokinetic and safety evaluation of the S-adenosylmethionine formulation MSI-195, and a commercial comparator. The study was broken into two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. The second stage was a single dose evaluation, targeting 26 male and female volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed by a food effect study on MSI-195. Plasma samples were collected and assayed for S-adenosylmethionine. Pharmacokinetic parameters were calculated using that data.
Detailed description
The study was focussed on the safety and pharmacokinetic evaluation of MSI-195; a novel patented formulation of S-adenosylmethionine. MSI-195 is a 400 mg dosage strength, tablet formulation comprising a core tablet, a seal coat and an enteric coat. The commercial comparator is SAM-e CompleteTM, manufactured by Pharmavite under the NatureMadeTM brand.
This study consisting of two stages. The first stage was an exploratory single ascending dose design of MSI-195 in 8 healthy normal male volunteers. The second stage was a more comprehensive single dose evaluation, targeting 26 male and female volunteers at set doses of MSI-195 and commercial comparator in a cross-over design followed by a food effect study on MSI-195.
Stage 1 design In each period of this stage of the study, ascending single doses of 400 mg, 800 mg and 1600 mg of MSI-195 was orally administered under fasted conditions, followed by 24 hours of blood draws at periodic intervals for the determination of plasma concentration of S-adenosylmethionine in a repeated-measure design. The drug administrations were separated by a wash-out of 7 calendar days.
Stage 2 design In the first 2 periods of this stage of the study, a single 800 mg dose of MSI-195 and a single 1600 mg dose of commercial comparator were orally administered under fasted conditions, in a 2-way crossover design. During the 3rd period, a single 800 mg dose of MSI-195 was administered under fed conditions to all subjects. The drug administrations were separated by a wash-out of 7 calendar days. For each dosing, subjects had periodic blood draws over a 24 hour period to determine the plasma concentration of S-adenosylmethionine as a function of time.
Male and female volunteers were included in the study. Subjects were in good health as determined by a medical history, complete physical examination (including vital signs), electrocardiogram (ECG), neurological examination and a panel of clinical laboratory tests.
Blood samples were collected and stored frozen until assayed. The samples were assayed for S-adenosylmethionine using a validated HPLC method with MS/MS detection.
For pharmacokinetic assessments, the main absorption and disposition parameters were calculated using a non-compartmental approach with a log-linear terminal phase assumption. The pharmacokinetic parameters of this trial were Cmax, Tmax, AUCT, AUC∞, AUCT/∞, Kel and T½el.
The safety parameters assessed included the occurrence of adverse events, the measurement of clinical laboratory parameters, vital signs, neurological function tests, physical examination and ECG
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Stage 1 - single ascending dose, Stage 2 - crossover and food effect study
| Arm | Type | Receives |
|---|---|---|
| 400 mg MSI-195 - SAD | Experimental | Drug: Ademetionine400 mg MSI-195 (within Stage 1, single ascending dose) |
| 800 mg MSI-195 - SAD | Experimental | Drug: Ademetionine800 mg MSI-195 (within Stage 1, single ascending dose) |
| 1600 mg MSI-195 -SAD | Experimental | Drug: Ademetionine1600 mg MSI-195 (within Stage 1, single ascending dose) |
| 800 mg MSI-195 - fasted | Experimental | Drug: Ademetionine800 mg MSI-195 fed (within Stage 2, cross-over comparison) |
| 1600 mg SAM-e Complete TM - fasted | Experimental | Drug: Ademetionine1600 mg SAM-e Complete (within Stage 2, cross-over comparison) |
| 800 mg MSI-195 - fed | Experimental | Drug: Ademetionine800 mg MSI-195- fed (within Stage 2, fed arm) |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Volunteers meeting all of the following criteria will be considered for enrollment in the study:
- The informed consent form must be signed by all volunteers, prior to their participation in the study.
Key exclusion criteria (19 listed)
- Volunteers presenting any of the following will not be included in the study:
- No subjects will be allowed to enroll in this study more than once (i.e. if the study is conducted with more than 1 group).
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 |
|---|---|---|
| Ademetionine | Drug | 1600 mg MSI-195 -SAD, 1600 mg SAM-e Complete TM - fasted, 400 mg MSI-195 - SAD, 800 mg MSI-195 - SAD, 800 mg MSI-195 - fasted, 800 mg MSI-195 - fed |
Primary outcome
Incidence and severity of treatment-related adverse events (safety and tolerability) as measured by vital signs, ECG, laboratory tests, neurological function tests, and the occurance of adverse events
Time frame: for 24 hours after dosing
Incidence and severity of treatment-related adverse events determined by changes from screening (baseline) of findings from physical examination, vital signs, ECG, laboratory tests, neurological function tests, and the occurance of adverse events.
Pharmacokinetics was evaluated by measuring the systemic plasma concentration of ademetionine
Time frame: for 24 hours after dosing
plasma concentrations of ademetionine were measured as a function of time using a validated bioanalytical assay
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
- Derived from this study: PubMed 33317621Cameron BR, Ferreira L, MacDonald ID. Pharmacokinetic study of a novel oral formulation of S-adenosylmethionine (MSI-195) in healthy subjects: dose escalation, food effect and comparison to a commercial nutritional supplement product. BMC Pharmacol Toxicol. 2020 Dec 14;21(1):88. doi: 10.1186/s40360-020-00466-7.
- Individual participant dataSharing planned: No
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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.
Eric Sicard, M.D. principal investigator
Algorithme Pharma Inc
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ademetionine in people with Major Depressive Disorder, run by MSI Methylation Sciences, Inc..
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 18 inclusion and 19 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: finished, as of the sponsor's last update on 10 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence and severity of treatment-related adverse events (safety and tolerability) as measured by vital signs, ECG, laboratory tests, neurological function tests, and the occurance of adverse events (time frame: for 24 hours after dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04623034, which also lists 1 linked publication.
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 10 Nov 2020.