Acute Intermittent Porphyria (AIP)Phase 1NCT03505853
A Study to Investigate the Interaction Between Givosiran and a 5-probe Drug Cocktail in Patients With Acute Intermittent Porphyria (AIP)
A Phase 1 study testing Givosiran and 5-probe cocktail in people with Acute Intermittent Porphyria (AIP) and Acute Hepatic Porphyria (AHP), run by Alnylam Pharmaceuticals at 1 site in Sweden.
Trial summary
The purpose of this study is to evaluate the effect of givosiran on the pharmacokinetics of the 5-probe cocktail of midazolam, caffeine, losartan, omeprazole, and dextromethorphan, and their metabolites, in asymptomatic patients with Acute Intermittent Porphyria. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Intermittent Porphyria (AIP), Acute Hepatic Porphyria (AHP), Porphyria, Acute Intermittent
- What is being tested?
- Givosiran and 5-probe cocktail
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSweden
- Study dates
- 26 Apr 2018to 10 Jan 2019
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 to 65 years old
- Weight between 45kg and 110kg, inclusive, if male
- Weight between 45kg and 100 kg, inclusive, if female
- Diagnosis of acute intermittent porphyria (AIP)
- Elevated urine PBG level
- Not be pregnant or breast feeding, and must be willing to use a highly effective method of contraception
Who cannot join
- Clinically significant abnormal laboratory results
- Experienced an acute porphyria attack within past 12 months
- History of multiple drug allergies, intolerances or sensitivities
- History of recurrent pancreatitis
- Received an experimental drug, within 3 months of dosing
- Donated or lost an excessive amount of blood within 60 days of dosing
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Drug-Drug Interaction Study to Investigate the Effect of Givosiran on the Pharmacokinetics (PK) of Midazolam, Caffeine, Losartan, Omeprazole, and Dextromethorphan in Patients With Acute Intermittent Porphyria (AIP) Who Are Asymptomatic High Excreters (ASHE)
The purpose of this study is to evaluate the effect of givosiran on the pharmacokinetics of the 5-probe cocktail of midazolam, caffeine, losartan, omeprazole, and dextromethorphan, and their metabolites, in asymptomatic patients with Acute Intermittent Porphyria.
- Conditions
- Acute Intermittent Porphyria (AIP), Acute Hepatic Porphyria (AHP), Porphyria, Acute Intermittent, Acute Porphyria
- Being tested
- Givosiran, 5-probe cocktail
- Keywords
- RNAi therapeutic, Porphyria, Acute Hepatic Porphyria (AHP), Acute Intermittent Porphyria (AIP)
- Medical subject headings
- Porphyria, Acute Intermittent, Coproporphyria, Hereditary, Porphyrias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GivosiranDrug
single dose of givosiran by subcutaneous (sc) injection
5-probe cocktailDrug
includes midazolam, caffeine, losartan, omeprazole, and dextromethorphan
| Study group | Role | What they receive |
|---|---|---|
| Givosiran with 5-probe cocktail | Experimental | Not described Receives: Drug: Givosiran; Drug: 5-probe cocktail |
What is being measured
The primary outcome is the main question the study is designed to answer.
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Area under the concentration-time curve (AUC)
Measured: Days 1 and 36
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Maximum plasma concentration (Cmax)
Measured: Days 1 and 36
Secondary outcomes (7)
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Area under the concentration-time curve (AUC)
Measured: Days 1 and 36
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Maximum plasma concentration (Cmax)
Measured: Days 1 and 36
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Terminal half-life (t1/2)
Measured: Days 1 and 36
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Volume of distribution (V/F)
Measured: Days 1 and 36
The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA)
Measured: Days 1, 8, and 36
The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP
Measured: Days 1, 8, and 36
Safety as evaluated by the proportion of subjects experiencing adverse events (AEs)
Measured: Day 1 - Day 92
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2018
- Study start26 Apr 2018
- Primary completion16 Nov 2018
- Study completion10 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Intermittent Porphyria (AIP)Studies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nader Najafian, MD, Study director, Alnylam Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03505853
- Sponsor's protocol ID
- ALN-AS1-004
- Status last verified
- Mar 2019
- First submitted
- 13 Apr 2018
- Last updated
- 12 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Drug-Drug Interaction Study to Investigate the Effect of Givosiran on the Pharmacokinetics (PK) of Midazolam, Caffeine, Losartan, Omeprazole, and Dextromethorphan in Patients With Acute Intermittent Porphyria (AIP) Who Are Asymptomatic High Excreters (ASHE)
- ClinicalTrials.gov ID
- NCT03505853
- Acronym / sponsor ID
- ALN-AS1-004
- Conditions
- Acute Intermittent Porphyria (AIP), Acute Hepatic Porphyria (AHP), Porphyria, Acute Intermittent, Acute Porphyria
- Keywords
- RNAi therapeutic, Porphyria, Acute Hepatic Porphyria (AHP), Acute Intermittent Porphyria (AIP)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Alnylam PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Apr 2018 (actual)
- Primary completion
- 16 Nov 2018 (actual)
- Study completion
- 10 Jan 2019 (actual)
- First posted
- 23 Apr 2018 (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.
The purpose of this study is to evaluate the effect of givosiran on the pharmacokinetics of the 5-probe cocktail of midazolam, caffeine, losartan, omeprazole, and dextromethorphan, and their metabolites, in asymptomatic patients with Acute Intermittent Porphyria.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Givosiran with 5-probe cocktail | Experimental | Drug: Givosiran, Drug: 5-probe cocktail |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18 to 65 years old
- Weight between 45kg and 110kg, inclusive, if male
- Weight between 45kg and 100 kg, inclusive, if female
- Diagnosis of acute intermittent porphyria (AIP)
- Elevated urine PBG level
Key exclusion criteria (6 listed)
- Clinically significant abnormal laboratory results
- Experienced an acute porphyria attack within past 12 months
- History of multiple drug allergies, intolerances or sensitivities
- History of recurrent pancreatitis
- Received an experimental drug, within 3 months of dosing
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 |
|---|---|---|
| Givosiransingle dose of givosiran by subcutaneous (sc) injection | Drug | Givosiran with 5-probe cocktail |
| 5-probe cocktailincludes midazolam, caffeine, losartan, omeprazole, and dextromethorphan | Drug | Givosiran with 5-probe cocktail |
Primary outcome
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Time frame: Days 1 and 36
Area under the concentration-time curve (AUC)
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Time frame: Days 1 and 36
Maximum plasma concentration (Cmax)
7 secondary outcomes
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Time frame: Days 1 and 36
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail metabolites
Time frame: Days 1 and 36
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Time frame: Days 1 and 36
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail
Time frame: Days 1 and 36
The pharmacodynamic (PD) effect of givosiran on urine levels of delta-aminolevulinic acid (ALA)
Time frame: Days 1, 8, and 36
The pharmacodynamic (PD) effect of givosiran on urine levels of Porphobilinogen (PBG) in patients with AIP
Time frame: Days 1, 8, and 36
Safety as evaluated by the proportion of subjects experiencing adverse events (AEs)
Time frame: Day 1 - Day 92
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 12 Mar 2019.
- 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.
Nader Najafian, MD study director
Alnylam Pharmaceuticals
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 Givosiran and 5-probe cocktail in people with Acute Intermittent Porphyria (AIP) and Acute Hepatic Porphyria (AHP), run by Alnylam Pharmaceuticals at 1 site in Sweden.
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 6 inclusion and 6 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 12 Mar 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 Sweden. 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?
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?
Profile of Pharmacokinetics (PK) of Cytochrome P450 (CYP) probe cocktail (time frame: Days 1 and 36). 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?
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 12 Mar 2019.