Healthy VolunteersPhase 1NCT02475317
Study to Assess the Relative Potency of Multiple Oral Doses of LUM001 and SHP626 in Overweight and Obese Adults as Assessed by Fecal Bile Acid Excretion
A Phase 1 study testing Maralixibat and Volixibat in people with Healthy Volunteers, run by Mirum Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to assess the relative potency of multiple oral doses of LUM001 and SHP626 administered for 7 days as assessed by fecal bile acid excretion in overweight and obese adult subjects. This study is designed to address the relative potency question for the first time in the same. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Maralixibat and Volixibat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2015to 1 Dec 2015
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- An understanding, ability, and willingness to fully comply with study procedures, study diet, and restrictions.
- Ability to voluntarily provide written, signed, and dated (personally or via a legally-authorized representative) informed consent/and assent as applicable to participate in the study.
- Aged 18-65 years inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
- Males who agree to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential (see Section 4.4 for details).
- Must be considered generally healthy. Health status is defined by the absence of evidence of any active or chronic disease (see Section 7.2.2.1 for details and exceptions) following the completion of a detailed medical and surgical history, a complete physical examination, vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.
- Must have a body mass index of 25.0-35.0 kg/m² inclusive with a body weight >63.5 kg (140 lbs at the first screening visit). This inclusion criterion will only be assessed at the first screening visit.
- All clinical laboratory parameters are within normal laboratory limit or not found to be clinically significant by the principal investigator.
- Ability to swallow a dose(s) of investigational product(s).
Who cannot join
- History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological, or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
- Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
- Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
- Significant illness, as judged by the investigator, within 2 weeks prior to the first dose of investigational product.
- Known history of alcohol or other substance abuse within the last year.
- Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to receiving the first dose of investigational product.
Show all 24Show fewer
- Within 30 days prior to the first dose of investigational product:
- Have used an investigational product (if elimination half-life is <6 days, otherwise 5 half-lives).
- Have been enrolled in a clinical study (including vaccine studies) that, in the investigator's opinion, may impact this Shire-sponsored study.
- Have had any substantial changes in eating habits or exercise routine, as assessed by the investigator
- Confirmed resting systolic blood pressure >145 mmHg or <89 mmHg, and diastolic blood pressure >95 mmHg or <59 mmHg.
- Twelve-lead ECG demonstrating QTc >460 milliseconds for male subjects or >470 milliseconds for female subjects at screening. If QTc exceeds 460 milliseconds for males or 470 milliseconds for females, the ECG should be repeated 2 more times and the average of the 3 QTc values should be used to determine the subject's eligibility
- A positive screen for drugs of abuse at screening or at Day -3 (check-in).
- Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. (1 alcohol unit=1 beer or 1 wine [5 oz/150 mL] or 1 liquor [1.5 oz/40 mL] or 0.75 oz alcohol).
- A positive HIV, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen.
- Use of tobacco (eg, smoking or chewing) or other nicotine-containing products (eg, gum, patch) in any form. Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
- Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6 oz [180 mL] cup of coffee, two 12 oz [360 mL] cans of cola, one 12 oz cup of tea, and three 1 oz [85 g] chocolate bars. Decaffeinated coffee, tea, and cola are not considered to contain caffeine.)
- Prior screen failure, randomization, participation, or enrollment in this study. If a subject has successfully completed a study using LUM001 or SHP626, they may participate in this study providing at least 30 days has passed since their last dose of these investigational products and they have successfully completed all screening procedures
- Current use of any medication (including over-the-counter, herbal, or homeopathic preparations) with the exception of those medications listed in Section 5.2.1. (Current use is defined as use within 14 days of the first dose of investigational product.)
- An inability to follow a standardized diet and meal schedule or inability to fast, as required during the study.
- Colonoscopy, barium enema, or other tests that require a bowel cleansing within 4 weeks prior to the first dose of investigational product.
- Subjects who report typically having less than 3 bowel movements per week or greater than 3 bowel movements per day.
- Use of antibiotics within 30 days prior to the first dose of investigational product.
- Use of bile acid sequestrants within 30 days prior to the first dose of investigational product
Trial locations and contacts
1 site in 1 country.
United States1 site
New Orleans Center for Clinical Research
Knoxville, Tennessee
About this study
Official title: A Randomized, Blinded, Placebo-controlled, Phase 1 Study to Assess the Relative Potency of Multiple Oral Doses of LUM001 and SHP626 in Overweight and Obese Adult Subjects, as Assessed by Fecal Bile Acid Excretion
The purpose of this study is to assess the relative potency of multiple oral doses of LUM001 and SHP626 administered for 7 days as assessed by fecal bile acid excretion in overweight and obese adult subjects. This study is designed to address the relative potency question for the first time in the same.
- Conditions
- Healthy Volunteers
- Being tested
- Placebo, Maralixibat, Volixibat
- Keywords
- Volunteer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Participants will receive placebo matched to maralixibat/volixibat orally for 7 days.
MaralixibatDrug
Also called LUM001
Participants will receive maralixibat in 10 mg, 20 mg, 50 mg or 100 mg doses.
VolixibatDrug
Also called SHP626
Participants will receive volixibat in 10 mg and 20 mg doses.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants will receive placebo matched to maralixibat 10 milligram (mg), 20 mg, 50 mg once daily (QD), 50 mg twice daily (BID), 100 mg liquid formulation and volixibat 10 mg, 20 mg capsule orally for 7 days. Receives: Drug: Placebo |
| Maralixibat 10mg | Experimental | Participants will receive maralixibat 10 mg liquid formulation orally QD for 7 days. Receives: Drug: Maralixibat |
| Volixibat 10mg | Experimental | Participants will receive volixibat 10 mg capsule orally QD for 7 days. Receives: Drug: Volixibat |
| Maralixibat 20mg | Experimental | Participants will receive maralixibat 20 mg liquid formulation orally QD for 7 days. Receives: Drug: Maralixibat |
| Volixibat 20mg | Experimental | Participants will receive volixibat 20 mg capsule orally QD for 7 days. Receives: Drug: Volixibat |
| Maralixibat 50mg | Experimental | Participants will receive maralixibat 50 mg liquid formulation orally QD for 7 days. Receives: Drug: Maralixibat |
| Maralixibat 50mg BID | Experimental | Participants will receive maralixibat 50 mg liquid formulation orally BID for 7 days. Receives: Drug: Maralixibat |
| Maralixibat 100mg | Experimental | Participants will receive maralixibat 100 mg liquid formulation orally QD for 7 days. Receives: Drug: Maralixibat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline of Fecal Bile Acid Excretion After Dosing (Day 6 and Day 7)
Fecal bile acid excretion was determined by the concentration of total bile acids in stool samples over each 24-hour collection window during the lead-in and treatment periods.
Measured: Baseline, Day 7
Secondary outcomes (12)
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An adverse event is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An AE (classified by preferred term) that occurred during the treatment period was considered a TEAE if it had a start date on or after the first dose of IMP; it had a start date before the date of the first dose of IMP, but increased in severity on or after the date of the first dose of the blinded IMP.
Measured: Baseline up to follow-up (up to 16 days)
Change From Baseline in Vital Signs (Supine Pulse Rate and Standing Pulse Rate) at Day 8 / End of Treatment (ET)
Supine Pulse Rate and Standing Pulse Rate were reported.
Measured: Baseline, Day 8
Change From Baseline in Vital Signs (Blood Pressure) at Day 8 / End of Treatment (EOT)
Supine Systolic Blood Pressure (Supine SBP); Standing Systolic Blood Pressure (Standing SBP); Supine Diastolic Blood Pressure (Supine DBP); Standing Diastolic Blood Pressure (Standing DBP) were reported.
Measured: Baseline, Day 8
Change From Baseline in 12-lead Electrocardiogram (ECG) - Heart Rate at Day 8 / End of Treatment (EOT)
Twelve-lead ECG was performed.
Measured: Baseline, Day 8
Change From Baseline in 12-lead ECG Intervals at Day 8
Twelve-lead ECG was performed. The corrected QT interval (QTc) was derived by Bazett formula (QTcB=QT/(RR)^1/2) and Fridericia formula (QTcF=QT/(RR)^1/3). PR Interval; QRS Interval; QT Interval; QTcB Interval; QTcF Interval, RR Intervals were reported.
Measured: Baseline, Day 8
Number of Participants with Clinically Meaningful Changes in Serum Biochemistry Laboratory Parameters
Number of participants with clinically meaningful changes in serum biochemistry laboratory parameters were reported.
Measured: Baseline up to Day 8
Number of Participants with Clinically Meaningful Changes in Coagulation and Hematology Parameters
Activated partial thromboplastin time (aPTT), hematocrit, hemoglobin, monocytes and erythrocytes were analyzed. Number of participants with clinically meaningful change in coagulation and hematology parameters were reported.
Measured: Baseline up to Day 8
Number of Participants With Clinically Meaningful Changes in Urinalysis Parameters
Number of participants with clinically meaningful changes in urinalysis parameters were reported.
Measured: Baseline up to Day 8
Change From Baseline in Total Serum Bile Acid Concentration at Day 7
Serum bile acid concentrations were determined using a validated liquid chromatography with tandem mass spectrometric detection (LC/MS/MS) method.
Measured: Baseline, Day 7
Change From Baseline in Serum Concentration of 7- alpha-hydroxy-4-cholesten-3-one (C4) at Day 7
Serum samples were assayed for C4 using a validated LC/MS/MS method.
Measured: Baseline, Day 7
Stool Hardness Measured by Bristol Stool Chart at Day 7
Stool hardness was assessed according to the Bristol Stool Chart, where 1 was the hardest and 7 was the softest form of stool. Types 3 and 4 were considered normal and types at either end of the scale were considered severe.
Measured: Day 7
Frequency of Bowel Movements at Day 7
Frequency of bowel movements were calculated by treatment group and by day.
Measured: Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2015 (estimated)
- Study start1 Jun 2015
- Primary completion1 Dec 2015
- Study completion1 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Mirum Pharmaceuticals, Inc.The sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mirum Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Mirum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02475317
- Sponsor's protocol ID
- SHP625-101
- Status last verified
- Apr 2019
- First submitted
- 10 Jun 2015
- Last updated
- 4 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Blinded, Placebo-controlled, Phase 1 Study to Assess the Relative Potency of Multiple Oral Doses of LUM001 and SHP626 in Overweight and Obese Adult Subjects, as Assessed by Fecal Bile Acid Excretion
- ClinicalTrials.gov ID
- NCT02475317
- Acronym / sponsor ID
- SHP625-101
- Conditions
- Healthy Volunteers
- Keywords
- Volunteer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Mirum Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Jun 2015
- Primary completion
- 1 Dec 2015 (actual)
- Study completion
- 1 Dec 2015 (actual)
- First posted
- 18 Jun 2015 (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.
The purpose of this study is to assess the relative potency of multiple oral doses of LUM001 and SHP626 administered for 7 days as assessed by fecal bile acid excretion in overweight and obese adult subjects. This study is designed to address the relative potency question for the first time in the same.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matched to maralixibat 10 milligram (mg), 20 mg, 50 mg once daily (QD), 50 mg twice daily (BID), 100 mg liquid formulation and volixibat 10 mg, 20 mg capsule orally for 7 days. |
| Maralixibat 10mg | Experimental | Drug: MaralixibatParticipants will receive maralixibat 10 mg liquid formulation orally QD for 7 days. |
| Volixibat 10mg | Experimental | Drug: VolixibatParticipants will receive volixibat 10 mg capsule orally QD for 7 days. |
| Maralixibat 20mg | Experimental | Drug: MaralixibatParticipants will receive maralixibat 20 mg liquid formulation orally QD for 7 days. |
| Volixibat 20mg | Experimental | Drug: VolixibatParticipants will receive volixibat 20 mg capsule orally QD for 7 days. |
| Maralixibat 50mg | Experimental | Drug: MaralixibatParticipants will receive maralixibat 50 mg liquid formulation orally QD for 7 days. |
| Maralixibat 50mg BID | Experimental | Drug: MaralixibatParticipants will receive maralixibat 50 mg liquid formulation orally BID for 7 days. |
| Maralixibat 100mg | Experimental | Drug: MaralixibatParticipants will receive maralixibat 100 mg liquid formulation orally QD for 7 days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- An understanding, ability, and willingness to fully comply with study procedures, study diet, and restrictions.
- Ability to voluntarily provide written, signed, and dated (personally or via a legally-authorized representative) informed consent/and assent as applicable to participate in the study.
- Aged 18-65 years inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit.
- Males who agree to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential (see Section 4.4 for details).
- Must be considered generally healthy. Health status is defined by the absence of evidence of any active or chronic disease (see Section 7.2.2.1 for details and exceptions) following the completion of a detailed medical and surgical history, a complete physical examination, vital signs, 12-lead ECG, hematology, blood chemistry, and urinalysis.
Key exclusion criteria (24 listed)
- History of any hematological, hepatic, respiratory, cardiovascular, renal, neurological, or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinical or laboratory assessments.
- Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures.
- Known or suspected intolerance or hypersensitivity to the investigational product(s), closely-related compounds, or any of the stated ingredients.
- Significant illness, as judged by the investigator, within 2 weeks prior to the first dose of investigational product.
- Known history of alcohol or other substance abuse within the last year.
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 |
|---|---|---|
| PlaceboParticipants will receive placebo matched to maralixibat/volixibat orally for 7 days. | Drug | Placebo |
| MaralixibatAlso: LUM001Participants will receive maralixibat in 10 mg, 20 mg, 50 mg or 100 mg doses. | Drug | Maralixibat 100mg, Maralixibat 10mg, Maralixibat 20mg, Maralixibat 50mg, Maralixibat 50mg BID |
| VolixibatAlso: SHP626Participants will receive volixibat in 10 mg and 20 mg doses. | Drug | Volixibat 10mg, Volixibat 20mg |
Primary outcome
Change From Baseline of Fecal Bile Acid Excretion After Dosing (Day 6 and Day 7)
Time frame: Baseline, Day 7
Fecal bile acid excretion was determined by the concentration of total bile acids in stool samples over each 24-hour collection window during the lead-in and treatment periods.
12 secondary outcomes
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Baseline up to follow-up (up to 16 days)
Change From Baseline in Vital Signs (Supine Pulse Rate and Standing Pulse Rate) at Day 8 / End of Treatment (ET)
Time frame: Baseline, Day 8
Change From Baseline in Vital Signs (Blood Pressure) at Day 8 / End of Treatment (EOT)
Time frame: Baseline, Day 8
Change From Baseline in 12-lead Electrocardiogram (ECG) - Heart Rate at Day 8 / End of Treatment (EOT)
Time frame: Baseline, Day 8
Change From Baseline in 12-lead ECG Intervals at Day 8
Time frame: Baseline, Day 8
Number of Participants with Clinically Meaningful Changes in Serum Biochemistry Laboratory Parameters
Time frame: Baseline up to Day 8
Number of Participants with Clinically Meaningful Changes in Coagulation and Hematology Parameters
Time frame: Baseline up to Day 8
Number of Participants With Clinically Meaningful Changes in Urinalysis Parameters
Time frame: Baseline up to Day 8
Change From Baseline in Total Serum Bile Acid Concentration at Day 7
Time frame: Baseline, Day 7
Change From Baseline in Serum Concentration of 7- alpha-hydroxy-4-cholesten-3-one (C4) at Day 7
Time frame: Baseline, Day 7
Stool Hardness Measured by Bristol Stool Chart at Day 7
Time frame: Day 7
Frequency of Bowel Movements at Day 7
Time frame: Day 7
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 4 Apr 2019.
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Screening Protocol
Pain
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.
Study Director study director
Mirum
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 Maralixibat and Volixibat in people with Healthy Volunteers, run by Mirum 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 8 inclusion and 24 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 4 Apr 2019. 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. Some participants in this study may receive a placebo. 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?
Change From Baseline of Fecal Bile Acid Excretion After Dosing (Day 6 and Day 7) (time frame: Baseline, 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 4 Apr 2019.