The objective of the study is to evaluate safety, tolerability, and pharmacokinetics (PK) of ALKS 6610 after single ascending oral doses in healthy adult subjects.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Pain
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tolerability / Safety Endpoints
Pharmacokinetic Endpoints
Secondary outcome
Pharmacodynamic Endpoints
Background summary
Chronic pain of moderate to severe intensity occurs in 19% of adult Europeans,
seriously affecting the quality of their social and working lives (Breivik et
al., 2006). More than 100 million people in the United States (~31% of the
adult population) are affected by chronic pain (National Research Council
2011). Opioids are effective treatments prescribed for acute and chronic pain.
An estimated 20% of patients presenting to physician offices with non-cancer
pain or pain-related diagnoses (including acute and chronic pain) receive an
opioid prescription (Daubresse et al., 2013). However, opioid pain medications
are associated with serious risks including overdose, respiratory depression,
constipation, sedation, and opioid use disorder. As such, there is an unmet
need for well-tolerated and effective therapies, including opioids with
improved safety characteristics, for the management of pain, especially chronic
pain. Additionally, central to the abuse-related side effects of opioid
analgesics is their rapid entry into the brain and activation of brain circuits
underlying reward and reinforcement (Volkow et al., 2000). Opioid analgesics
with slower or reduced brain exposure have been postulated to have lower
potential of abuse and addiction (Miyazaki et al., 2017). ALKS 6610 was
designed to be a partial µ-opioid receptor (MOR) agonist with a preference
toward G-protein coupled intracellular signalling, with low levels of β-
arrestin recruitment and a predicted reduced rate of brain penetration. The
mechanism of action and available pharmacology data suggest that ALKS 6610 has
the potential to improve the treatment of pain by providing opioid-like
analgesia with an improved safety profile, including lower abuse potential and
reduced risk of respiratory depression, compared to currently approved opioid
agonists.
This is the first study with ALKS 6610 in humans, designed to assess the
safety, tolerability, pharmacokinetics and pharmacodynamics of single ascending
doses with a pilot evaluation of food effect. The study results will be used to
support further clinical development of ALKS 6610.
Study objective
The objective of the study is to evaluate safety, tolerability, and
pharmacokinetics (PK) of ALKS 6610 after single ascending oral doses in healthy
adult subjects.
Study design
This study will be a randomized, single-centre, double-blind,
placebo-controlled single ascending dose (SAD) study in healthy adult subjects
to evaluate the safety, tolerability, PK, and PD of ALKS 6610.
Intervention
Capsules of 25mg, 75mg, 150mg, 300mg, 600mg, 900mg, 1200mg ALKS 6610 or
placebo.
Study burden and risks
The risks associated with the administration of ALKS 6610 to humans have not
yet been identified, since this will be the first
administration in humans. All study drug administrations will be performed ¡n
the clinic under medical supervision. The proposed
FIH study consists in a single dose administration, with close monitoring of
participants' vital functions during 96h
following administration. The monitoring of vital function includes the
monitoring of respiratory rate, oxygen saturation, end-tidal CO2, ECG, pupil
size, blood pressure and heart rate. Thus, the subjects will be closely
monitored for any adverse signs during all dose levels.
Therefore careful observation and medical management will minimize any
associated risk in this study. For all dose levels, the
first administrations will be dosed using a sentinel approach: the first two
subjects will be randomized to receive 1 placebo and 1
active and dosed with a 24 hour observation period prior to dosing the
remaining subjects of the dose level. In case of an emergency suggesting opioid
overdose with ALKS 6610, supportive care measures with or without naloxone
followed by close monitoring for several hours are indicated.
Healthy subjects in the current study fall in a low risk category for
complications of COVID-19, the disease caused by the SARSCoV-2 virus. To
prevent SARS-CoV-2 infections among trial participants, measures and procedures
based on the advice issued by the Dutch Centre for Infectious Disease Control
(RIVM) and COVID-19 measures declared by the Dutch government will be adhered
to as outlined in CHDR SOP GGECOVID.
Winter Street 852
Waltham MA 02451
US
Winter Street 852
Waltham MA 02451
US
Listed location countries
Age
Inclusion criteria
1. Signed informed consent prior to any study-mandated procedure
2. Ability to communicate well with the Investigator in the Dutch language and
willing to follow the procedures and comply with study restrictions as outlined
in the protocol
3. Male or female age >=18 years and <=60 years old at the time of informed
consent
4. Body mass index (BMI) >=18 and <30 kg/m2 at Screening
Exclusion criteria
1. Clinically significant illness or disease (e.g. psychiatric disorders,
disorders of the gastrointestinal tract, liver [including Gilbert*s syndrome],
kidney [including nephrectomy], respiratory system, endocrine system,
haematological system, neurological system, or cardiovascular system,
infection, or subjects who have a congenital abnormality in metabolism) within
8 weeks of dosing, or any clinically abnormal symptom or organ impairment, as
judged by the Investigator, found by medical history, physical examinations,
vital signs, electrocardiogram (ECG) finding, or either abnormal laboratory
values or laboratory test results at Screening or Baseline (either Day -2 or
Day -1)
2. Presence of any condition in which an opioid is contraindicated (e.g.
respiratory depression, asthma, sleep apnea, ileus, etc.), unless regarded not
clinically significant by the Investigator
3. Females who are breastfeeding or pregnant at Screening or Baseline (Day -2)
(documented by a negative β human chorionic gonadotropin [β-hCG] or human
chorionic gonadotropin [hCG] test with a minimum sensitivity of 25 IU/L or
equivalent units of β-hCG [or hCG]). A negative urine pregnancy test is
required before the administration of the first dose per cohort
4. Females of childbearing potential. NOTE: All females will be considered to
be of childbearing potential unless they are postmenopausal (amenorrheic for at
least 12 consecutive months, and without other known or suspected cause) or
have been sterilized surgically (i.e. bilateral tubal ligation, total
hysterectomy, or bilateral oophorectomy, all with surgery at least 6 weeks
before dosing)
5. Any history of gastrointestinal surgery that may affect PK profiles of ALKS
6610 (e.g. hepatectomy, digestive organ resection) or other conditions that may
impact absorption (malabsorption syndrome, inflammatory bowel disease, etc.) at
Screening
6. A prolonged QT/QTc interval (QTcF >450 ms in males, and QTcF >470 ms in
females) demonstrated on ECG at Screening or Baseline (either Day -2 or Day
-1). A history of risk factors for torsade de pointes (e.g. heart failure,
hypokalaemia, family history of long QT Syndrome)
7. Left bundle branch block at Screening or Baseline (either Day -2 or Day -1)
8. Systolic blood pressure (BP) >140 or <90 mmHg or diastolic BP >90 or <50
mmHg at Screening or Baseline (either Day -2 or Day -1) or history of
clinically relevant orthostatic hypotension
9. Heart rate less than 45 beats per minute (bpm) or more than 100 bpm at
Screening or Baseline (either Day -2 or Day -1)
10. History of myocardial infarction, ischemic heart disease, or cardiac
failure at Screening
11. History of clinically significant arrhythmia or uncontrolled arrhythmia as
determined by the Investigator at screening
12. Subjects who have demonstrated allergic reactions (e.g. food, drug, atopic
reactions or asthmatic episodes) which, in the opinion of the Investigator,
interfere with their ability to participate in the trial
13. Positive Hepatitis A antibodies (HAV IgM), Hepatitis B surface antigen
(HBsAg), Hepatitis B antibodies (Anti-HBc), Hepatitis C antibodies (HCV Ab), or
human immunodeficiency virus antibody (HIV Ab) at Screening
14. Use of nicotine containing products within 2 weeks before the first dose of
study drug (Day 1)
15. History of opioid use disorder per Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition (DSM-5) classification, or other drug/substance
or alcohol dependency or abuse before Screening, or those who have a positive
drug test or alcohol test at Screening or Baseline (Day -2)
16. Use of prescription and non-prescription medications, herbal and
nutritional supplements within 2 weeks prior to dosing or 5 half-lives,
whichever is longer. Exceptions will only be made with approval of the
Principal Investigator and Alkermes* Medical Monitor
17. Any history of lifetime suicidal ideation or behaviour, confirmed by a
Columbia Suicide Severity Rating Scale (C-SSRS) response of *Yes* to questions
4 or 5 at Screening
18. Currently enrolled in another clinical study, used any investigational drug
or device within 3 months prior to dosing, or having participated in more than
4 investigational drug studies within 1 year prior to Screening
19. Receipt of blood products within 4 weeks, blood donation or blood loss of
>250 mL within 8 weeks, or donation of plasma within 1 week of first ALKS 6610
dose (Day 1)
20. Subject has any finding that may compromise the safety of the subject
(e.g., difficulty with venous access) or affect their ability to adhere to the
protocol requirements
21. Is employed by Alkermes, the Investigator or study site, (permanent,
temporary contract worker, or designee responsible for the conduct of the
study) or is immediate family* of an Alkermes, Investigator, or study site
employee
22. Positive SARS-CoV-2 PCR analysis prior to first dosing.
* Immediate family is defined as a spouse, parent, sibling, or child, whether
biological or
legally adopted
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
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-004075-39-NL |
| CCMO | NL71886.056.19 |